Sure, I am speculating, but the damn secrets are and should be unfolding, as many try to save our sorry souls, and bodies, the apocalypse horsemen are riding.
How life began is not the issue, how life ends it the issue.
De novo science seems to want to end it.
From beginning to end, Alpha and Omega..........
How many of us have Omega cells, now?
How many of us have Alpha, the integrated?
You know I started researching Morgellons, and it is now to the point where either one strives for survival, or gives into the New Dawning bs.
For the new day, will change it all, I have no idea what that means, but, either we blow these popstand jokers, and get to the truth of the matter, it will no matter what we believe, it will matter as to whether we can survive this phony, unitiarian, one cell, one dna, one religion, one race, that Universal support for the controller of the earth, Sa Tan himself.
When our answer, is from other places, when we can accept our ancestors for who they are, when we can reach back up to them, our homeland, our fathers, for the line of true descent is from our FATHERS!
It was Eve, who wanted to know, just wanted to understand, just wanted to have the knowledge, and once Eve found the knowledge she knew the price she had to pay, and women are paying the price daily!
But, it was the Fathers who were supposed to guide us, to let us know that knowledge is powerful, that knowledge is truth, that knowledge shows us the way, that knowledge is Painful!
If we could only hear the women, the ones who provide the skirt of life and protection for the children who live in a different world than our own.
Those children who will be artificial, who will live forever, as mere objects as mere, cloned images of our ancestors, as mere children of the sun, stars, planets, and interstellular dust is what made us, made the planets, made the highwater, the low water, the higher realms we cannot see but believer are there, the invisible. We cannot see the other dimensions, we can only believe they are there. And in that is the power we cannot comprehend, cannot measure, cannot see, but, yet, we know that it is in reaching out, in gathering in the fallen, the broken, the lost, that that is not our goal, but, to know that we are driven to make the wrongs, right, to give to the poor in a way that will uplift them, and not control them, but will uplift them out of poverty, out of dead thinking, out of the hell, they endure. for the meek know, they know that what they have now, is nothing, nothing, nothing.
The sick know that what we have is nothing, nothing, nothing, ' So to begin again, means we have to see their nothing~! We have to feel it, see it, hear it, we have to " walk a mile in their moccasins" We have to feel the smallpox, the rickets, the herpes, the dementias, the leprosy, the syphillis, the lymes, the morgellons, the virus from our planets, from our beginnings, from our homelands, from our ancestors, we have to feel their growing pains, we have to love them! To understand!
Last Edit: Apr 10, 2010 16:34:04 GMT -5 by skyship
I believe we are all in this struggle, Morgellonites are the roosters! We are the protocell, we are the experiments, the ones who try to explain, the ones who try to understand this rock in the middle, of our lifes, this rock that prevents us from enjoying our lives, our children, and yet, we see far beyond, what is considered our reality.
We see beyond, we hear beyond, we know we are catalysts as those inside of us are, mere objects, inorganic life that makes the unreal real and the real, unreal.
We see the truth, we see the light, the altered light, the veil, we see beyond the mere daily grind, we see beyond, and we are slaughtered for it, how many before us, knew, and they were beheaded, sent into the fire, for we are merely wood, and Satan is the fire. Do we fall for the joker's Rose? Do we fall for the knowledge trap again? No...............................................................
I think our own phosphorus coupled with wireless energy is used for quorum sensing.
Wireless energy frequencies are being used for the assembly. It is changing our natural states into magnetic states , coupling us together. We are sensing now more like the bee's , the waves are connecting us and our body is receiving instructions.
So, the bioilluminescense is key here to the spark, phosphorus, seems white phosphorus was used in Gaza, a while back...... for good or evil?
well, in the protocell, seems something was substituted, wonder if it was basalt.
Now, this is in the Molecular Institute:
A model for the origin of stable protocells in a primitive alkaline ocean
aInstitute for Molecular and Cellular Evolution and Department of Chemistry, University of Miami, 521 Anastasia Avenue, Coral Gables, Florida 33134, USA
When a mixture of the eighteen proteinous amino acids are suitably heated in the dry state with seawater salts, a copolyamino acid results. One fraction of this polymer is found, through isoelectric focusing, to consist of a mixture of acidic and basic proteinoids, each of sharply limited heterogeneity. When one fraction of the seawater proteinoid is dissolved in hot water, and the solution is cooled, proteinoid microspheres result. These have properties in common with simpler types, but are also stable at pH values to 9, in common with microspheres prepared by mixing acidic and basic proteinoids. These processes thus constitute a simple model for the origin of a protocell stable in a primitive alkaline ocean.
To evaluate the effects of phosphorus on differentiation of evolved basaltic magmas, a series of one-atmosphere experiments on a ferrobasaltic composition were carried out over a range of P2O5 contents and at oxygen fugacities from 2 log10 units below to 2 log10 units above the fayalite-magnetite-quartz (FMQ) buffer curve. The experiments were performed isothermally, the investigated variables being the amount of added P2O5 and the oxygen fugacity (fo2). The results confirm the high solubility of phosphorus in basaltic magmas and show that, at fixed temperature, the progressive addition of phosphorus causes:
1. (1) the disappearance of olivine at reducing conditions,
2. (2) the disappearance of magnetite at oxidising conditions,
3. (3) the stabilisation of pigeonite throughout the studied range of fo2,
4. (4) an increase in the modal plagioclase/pyroxene ratio, and
5. (5) increased melt proportion and large changes in the composition of the coexisting melt, in particular the SiO2 content.
The destabilisation of magnetite with increasing P2O5 content may be accounted for by the formation of Fe3+(PO4)3− complexes, rather than by a large change of the redox ratio of the melt; we suggest that the formation of Fe3+(PO4)3− complexes dominates that of P-O-M complexes (where M is a network-modifying cation). The effect of P on the modal proportions of plagioclase and pigeonite may help to explain the mineralogy of some anorthositic rocks and KREEP basalts, as well as the presence of pigeonite as an intercumulus phase in the Skaergaard intrusion (resulting from enrichment of the trapped liquid in phosphorus). These new results thus provide insights into the effects of phosphorus in lunar and terrestrial systems, as well as providing information regarding the structural role of phosphorus in silicate melts.
When we say fibers are in the rain and air, we are correct.
The Rain falls mainly on the Plain, and My Fair Lady.
Christner et al. have examined snow and rain for the presence of nucleators. As reported in the Science paper, they found that 70 to 100% of the nucleators in snow that were active at higher temperatures were biological, and a majority of those were live bacteria. It turns out that most of these bacteria are plant pathogens, specifically Pseudomonas syringae. They infect, but don't necessarily kill plants, spending much of their time there, but they can be swept up into the atmosphere when conditions are favorable, where they drift with the winds aloft, later to form the core of rain drops or snowflakes, and then fall back down to Earth. Those that land on plants reproduce there, and then can be blown back up into the atmosphere, where they can become part of the precipitation cycle all over again.
.........."So, these plant pathogens may contribute to rainy -- or dry -- conditions anywhere in the world, and there may be feedback loops. If an area is suffering from drought, vegetation may be sparse, and thus populations of these rain-inducing bacteria may be sparse, thus leading to less rain, less vegetation, and so on. It's possible that this kind of feedback is in part responsible for the droughts in Africa and Australia, according to Sands and colleagues. That means they can have continental, and hence perhaps in turn even global climate effects."
These are in the cloud seeding all over the earth and are infecting plants, does not kill plant? Well, if the skin of the plant is infected, so are we, if the skin of the frog, the fish, the tree, so are we, if the skin of the grass, so are we......
The black wind that has been talked about, the terror is in the spore. The black spore of life.
That spore and melanin work pretty well in hydrocarbons, pahs or buckyballs.
How is it released in form of spore?
Beware the fogs of November:
The occurrence of airborne biological particles (bacteria, yeasts and moulds) in fog water and the influence of temperature and fog chemical composition and acidity on their concentration are described in this paper. Our results show that the concentration of airborne bacteria and yeasts is enriched in foggy conditions up to two orders of magnitude compared to clear air conditions, while concentration of moulds is not influenced by the presence of fog. These results support the hypothesis that fog droplets act as culture media for airborne biological particles, i.e. they represent an atmospheric source of secondary biological particles. Biological aerosol particles; cloud condensation nuclei; fog chemistry; aerobiology
cdc12p, a Protein Required for Cytokinesis in Fission Yeast, Is a Component of the Cell Division Ring and Interacts with Profilin
.."As in many other eukaryotic cells, cell division in fission yeast depends on the assembly of an actin ring that circumscribes the middle of the cell. Schizosaccharomyces pombe cdc12 is an essential gene necessary for actin ring assembly and septum formation. Here we show that cdc12p is a member of a family of proteins including Drosophila diaphanous, Saccharomyces cerevisiae BNI1, and S. pombe fus1, which are involved in cytokinesis or other actin-mediated processes. "
....."Finally, we found that cdc12 and cdc3 mutants show a syntheticlethal genetic interaction, and a proline-rich domain of cdc12p binds directly to profilin cdc3p in vitro, suggesting that one function of cdc12p in ring assembly is to bind profilin.".............
cdc12p is a member of a family of proteins including Drosophila diaphanous, Saccharomyces cerevisiae BNI1, and S. pombe fus1, which are involved in cytokinesis or other actin-mediated processes. "
Profilin is an actin-binding protein involved in the dynamic turnover and restructuring of the actin cytoskeleton. It is found in all eukaryotic organisms in most cells.Profilin is important for spatially and temporally controlled growth of actin microfilaments, which is an essential process in cellular locomotion and cell shape changes. This restructuring of the actin cytoskeleton is essential for processes such as organ development, wound healing, and the hunting down of infectious intruders by cells of the immune system.
Profilin also binds sequences rich in the amino acid proline in diverse proteins. While most profilin in the cell is bound to actin, profilins have over 50 different binding partners. Many of those are related to actin regulation, but profilin also seems to be involved in activities in the nucleus such as mRNA splicing.
Profilin binds some variants of membrane phospholipids (Phosphatidylinositol (4,5)-bisphosphate and Inositol triphosphate). The function of this interaction is the sequestration of profilin in an "inactive" form, from where it can be released by action of the enzyme phospholipase C.
Profilin is the major allergen present in birch, grass, and other pollen
History of profilin discovery
Profilin was first described by Uno Lindberg and co-workers in the early 1970's as the first actin monomer binding protein. It followed the realization that not only muscle, but also non-muscle cells, contained high concentrations of actin, albeit in part in an unpolymerized form.Profilin was then believed to sequester actin monomers (keep them in a pro-filamentous form), and release them upon a signal to make them accessible for fast actin polymer growth.
====================== EntrezGene summary for DIAPH1:
This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. (provided by RefSeq)
UniProtKB/Swiss-Prot: DIAP1_HUMAN, O60610 Function: Acts in a Rho-dependent manner to recruit PFY1 to the membrane. Required for the assembly of F-actin structures, such as actin cables and stress fibers. Nucleates actin filaments. Binds to the barbed end of the actin filament and slows down actin polymerization and depolymerization. Required for cytokinesis, and transcriptional activation of the serum response factor. DFR proteins couple Rho and Src tyrosine kinase during signaling and the regulation of actin dynamics. Functions as a scaffold protein for MAPRE1 and APC to stabilize microtubules and promote cell migration (By similarity). In hearing it may play a role in the regulation of actin polymerization in hair cells
"The story begins back in the early 1990s with the analysis of Rho, then a newly described member of the Ras superfamily of small guanosine triphosphatases (GTPases). In Swiss 3T3 fibroblasts, it was shown that Rho can be activated by the addition of extracellular ligands [for example, lysophosphatidic acid] and that Rho activation leads to the assembly of contractile actin-myosin filaments (stress fibers) and of associated focal adhesion complexes (Fig. 1, C and D) (1). It was concluded that Rho acts as a molecular switch to control a signal transduction pathway that links membrane receptors to the cytoskeleton. Rac, the next member of the Rho family to be analyzed, could be activated by a distinct set of agonists (for example, platelet-derived growth factor or insulin), leading to the assembly of a meshwork of actin filaments at the cell periphery to produce lamellipodia and membrane ruffles (Fig. 1E)"........
"Rho, Rac, and Cdc42 have been reported to regulate the c-Jun NH2-terminal kinase (JNK) and the p38 mitogen-activated protein (MAP) kinase cascades and thereby regulate gene transcription in a more direct way than through their effects on adhesion complexes"
."In an apparently JNK- and p38-independent manner, the GTPases have been reported to stimulate transcription from the cyclin D promoter and to activate the serum response transcription factor (SRF) (18, 19). Rho GTPases trigger progression of the G1 phase of the cell cycle when introduced into quiescent fibroblasts, and their activities are essential for serum-induced G1 progression and for Ras-induced cell transformation (20, 21).".............
The human R-ras gene was isolated by low-stringency hybridization with a v-H-ras probe. The predicted 218 amino acid R-ras protein has an amino-terminal extension of 26 residues compared with H-ras p21, and shows 55% amino acid identity; conserved domains include the p21 GTP-binding site and the carboxy-terminal membrane localization sequence. R-ras has at least six exons, with the position of the first intron conserved relative to the Drosophila ras64B and Dictyostelium ras genes; there is no similarity in the exon-intron structure of the R-ras gene and of the mammalian H-, K-, and N-ras proto-oncogenes. Cloned mouse R-ras cDNAs exhibit 88% nucleotide and 94.5% predicted amino acid identity to human R-ras. Human R-ras was localized to chromosome 19, a site different from ras p21 genes. Mouse R-ras is syntenic with c-H-ras on chromosome 7.
Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK. firstname.lastname@example.org Abstract
Phosphoinositide 3-OH kinase (PI 3-kinase) provides cells with a survival signal that allows them to withstand apoptotic stimuli. Many tumour cells display elevated levels of PI 3-kinase products as a result of deletion of the phosphatase PTEN, activation of Ras or expression of autocrine growth factors. As a result they are relatively resistant to apoptosis. The mechanisms for PI 3-kinase survival signalling are becoming clear. The principal mediator is Akt, a PI 3-kinase activated protein kinase. Akt has direct effects on the apoptosis machinery, for example targeting the pro-apoptotic Bcl-2 related protein, BAD. It also affects the transcriptional response to apoptotic stimuli, for example by acting on Forkhead factors and also influence the activity of the p53 family. In addition, novel connections between the metabolic effects of Akt and its control of survival have recently been made.
We report here that Ras proteins play a key role in integrating mitogenic signals with cell cycle progression through G1. Ras is required for cell cycle progression and activation of both Cdk2 and Cdk4 until approximately 2 h before the G1/S transition, corresponding to the restriction point. Analysis of Cdk-cyclin complexes indicates that Ras signaling is required both for induction of cyclin D1 and for downregulation of the Cdk inhibitor p27KIP1. Constitutive expression of cyclin D1 circumvents the requirement for Ras signaling in cell proliferation, indicating that regulation of cyclin D1 is a critical target of the Ras signaling cascade.
where dimer comes in. These are artificial ligands. Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules
G-protein–coupled receptors (GPCRs) are the largest family of transmembrane signaling proteins in the human genome. Events in the GPCR signaling cascade have been well characterized, but the receptor composition and its membrane distribution are still generally unknown. Although there is evidence that some members of the GPCR superfamily exist as constitutive dimers or higher oligomers, interpretation of the results has been disputed, and recent studies indicate that monomeric GPCRs may also be functional. Because there is controversy within the field, to address the issue we have used total internal reflection fluorescence microscopy (TIRFM) in living cells to visualize thousands of individual molecules of a model GPCR, the M1 muscarinic acetylcholine receptor. By tracking the position of individual receptors over time, their mobility, clustering, and dimerization kinetics could be directly determined with a resolution of ~30 ms and ~20 nm. In isolated CHO cells, receptors are randomly distributed over the plasma membrane. At any given time, ~30% of the receptor molecules exist as dimers, and we found no evidence for higher oligomers. Two-color TIRFM established the dynamic nature of dimer formation with M1 receptors undergoing interconversion between monomers and dimers on the timescale of seconds.
INSM1 functions as a transcriptional repressor of the neuroD/b2 gene through the recruitment of cyclin D1 and histone deacetylases
NSM1/IA-1 (insulinoma-associated 1) is a developmentally regulated zinc-finger transcription factor, exclusively expressed in the foetal pancreas and nervous system, and in tumours of neuroendocrine origin. We have identified an INSM1 binding site in the neuroD/b2 promoter and demonstrated transcriptional repressor activity of INSM1 by transient transfection assay. A chromatin immunoprecipitation assay confirmed that in vivo INSM1 is situated on the promoter region of the neuroD/b2 gene. In an attempt to elucidate the molecular mechanism of transcriptional repression by the INSM1 gene, cyclin D1 was identified as an interacting protein by using a 45-day-old human foetal brain cDNA library and a yeast two-hybrid screen. The physical association between INSM1 and cyclin D1 was confirmed by in vitro and in vivo pull-down assay. Cyclin D1 co-operates with INSM1 and suppresses neuroD/b2 promoter activity.
--------------------------- Formin-induced nucleation of actin filaments
Formins are proteins best defined by the presence of the unique, highly conserved formin homology domain 2 (FH2). FH2 is necessary and sufficient to nucleate an actin filament in vitro. The FH2 domain also binds to the filament’s barbed end, modulating its elongation and protecting it from capping proteins. FH2 itself appears to be a processive cap that walks with the barbed end as it elongates.
Abbreviations: DAD, Diaphanous autoregulatory domain; FH, Formin homology domain; GBD, GTPase binding domain; hDia, human homologue of Drosophila Diaphanous; mDia, mouse homologue of Drosophila Diaphanous; WASP, Wiscott–Aldrich syndrome protein
Now, does this refer to the diaphanous of the drosophila? for actin binding anywhere in the human body? where does WASP, the Wiscott-Aldrich syndrome protein come in here?
They are talking about the barbed ends of dna here. so what spermatozoa are they talking about, human male or the the spermatozoa of the drosophila? That would explain the bugs in us, the dang fruit fly protein.
FH2 domain also binds to the filament’s barbed end, modulating its elongation
So it seems an elongation of dna is going on, supposedly to be immortal? mmmmm
in other words a capping would make the dna circular, whereas elongation would extend the dna length. I do not know why this needs to be done, other than selective elongation factor, to elongate life itself. So, why some ends are capped and others are not is the question.
What is the substitute FH2?
Looks like they had to match human cells to angiosperms, from plants!
The many faces of actin: matching assembly factors with cellular structures
Actin filaments are major components of at least 15 distinct structures in metazoan cells. These filaments assemble from a common pool of actin monomers, but do so at different times and places, and in response to different stimuli. All of these structures require actin-filament assembly factors. To date, many assembly factors have been identified, including Arp2/3 complex, multiple formin isoforms and spire. Now, a major task is to figure out which factors assemble which actin-based structures. Here, we focus on structures at the plasma membrane, including both sheet-like protrusive structures (such as lamellipodia and ruffles) and finger-like protrusions (such as filopodia and microvilli). Insights gained from studies of adherens junctions and the immunological synapse are also considered.
..."Actin filament nucleation is unfavourable; therefore, nucleation factors are required to initiate assembly of any actin-based structure1. At present, there are three known classes of nucleation factor: Arp2/3 complex, formin proteins and spire."........
================== What is Wiskott Aldrich syndrome? A chromosome is an organised structure of DNA (the genetic material) and protein that is found in cells of the body. In humans, the so-called X and Y-chromosomes determine the sex, but carry also other genetic information.
Wiskott Aldrich syndrome is caused by an abnormality of a gene located on the X chromosome. This gene is responsible for the production of a protein, Wiskott Aldrich protein, which is part of the structure responsible for the cellular “scaffolding” enabling the shape and movement of the cells (cytoskeleton). The cytoskeleton is also fundamental for the cell to be able to capture substances or organisms (endocytosis) or for actions linked to the body’s defense system. This means that patients suffering from Wiskott Aldrich syndrome have different symptoms, depending on the cells affected, such as decrease in the number of platelets and increased bleeding, eczema, repeated infections, or increased risk for development of autoimmune diseases and tumours. Wiskott Aldrich syndrome is chronically debilitating and life-threatening.
So they came up with a disease, that clarifies the protein.
============== How is this medicine expected to work? Lentiviral vector containing the human Wiskott Aldrich syndrome protein gene is a medicinal product that uses a virus to carry the normal gene necessary for the production of the Wiskott Aldrich protein. A virus is a small organism capable of introducing genetic material into the cells. The type of virus (lentivirus) used in this medicinal product is modified in order to avoid causing any disease in humans............
We use a virus to introduce this? seems this lentivirus is what caused a crippling disease in Ms. McClain.........
Note: the virus is put in the medicine!
Here is the kicker!
What is the stage of development of this medicine?
The effects of lentiviral vector containing the human Wiskott Aldrich syndrome protein gene were evaluated in experimental models. At the time of submission of the application for orphan designation, no clinical trials in patients with Wiskott Aldrich syndrome condition were initiated.
Lentiviral vector containing the human Wiskott Aldrich syndrome protein gene was not authorised anywhere worldwide for Wiskott Aldrich syndrome or designated as orphan medicinal product elsewhere for this condition, at the time of submission.
According to Regulation (EC) No 141/2000 of 16 December 1999, the Committee for Orphan Medicinal Products (COMP) adopted on 7 December 2005 a positive opinion recommending the grant of the above-mentioned designation.
Opinions on orphan medicinal product designations are based on the following three criteria: • the seriousness of the condition; • the existence of alternative methods of diagnosis, prevention or treatment; • and either the rarity of the condition (affecting not more than five in 10,000 people in the Community) or the insufficient returns on investment Designated orphan medicinal products are products that are still under investigation and are considered for orphan designation on the basis of potential activity. An orphan designation is not a marketing authorisation. As a consequence, demonstration of the quality, safety and efficacy is necessary before a product can be granted a marketing authorisation.
We determined a crystal structure of bovine Arp2/3 complex, an assembly of seven proteins that initiates actin polymerization in eukaryotic cells, at 2.0 angstrom resolution. Actin-related protein 2 (Arp2) and Arp3 are folded like actin, with distinctive surface features.Subunits ARPC2 p34 and ARPC4 p20 in the core of the complex associate through long carboxyl-terminal alpha helices and have similarly folded amino-terminal alpha/beta domains.ARPC1 p40 is a seven-blade beta propeller with an insertion that may associate with the side of an actin filament. ARPC3 p21 and ARPC5 p16 are globular alpha-helical subunits.We predict that WASp/Scar proteins activate Arp2/3 complex by bringing Arp2 into proximity with Arp3 for nucleation of a branch on the side of a preexisting actin filament.
for each protein created many parts or compartmentalizations of the protein are present, so it has to be broken down until you find where the protein or enzyme or molecule began and from what species of organism, plant or animal insect or mineral.
So, it seems the the cytoskeleton cells and components all involved with the actin filament.
Now, this involves 7 components!
Last Edit: Apr 22, 2010 13:45:06 GMT -5 by skyship
ARPC1 p40 is a seven-blade beta propeller with an insertion that may associate with the side of an actin filament. ARPC3 p21 and ARPC5 p16 are globular alpha-helical subunits. ARPC1 p40
The Arp2/3 complex is a conserved seven-subunit actin-nucleating machine activated by WASp (Wiskott Aldrich syndrome protein). Despite its central importance in a broad range of cellular processes, many critical aspects of the mechanism of the Arp2/3 complex have yet to be resolved. In particular, some of the individual subunits in the complex have not been assigned clear functional roles, including p40/ARPC1.,,,,,
..."Here, we dissected the structure and function of Saccharomyces cerevisiae p40/ARPC1, which is encoded by the essential ARC40 gene, by analyzing 39 integrated alleles that target its conserved surfaces. We identified three distinct sites on p40/ARPC1 required for function in vivo: one site contacts p19/ARPC4, one contacts p15/ARPC5, and one site resides in an extended structural “arm” of p40/ARPC1. Using a novel strategy, we purified the corresponding lethal mutant Arp2/3 complexes from yeast and compared their actin nucleation activities. Lethal mutations at the contact with p19/ARPC4 specifically impaired WASp-induced nucleation. In contrast, lethal mutations at the contact with p15/ARPC5 led to unregulated (“leaky”) nucleation in the absence of WASp. Lethal mutations in the extended arm drastically reduced nucleation, and the same mutations disrupted the ability of the purified p40/ARPC1 arm domain to bind the VCA domain of WASp. Together, these data indicate that p40/ARPC1 performs at least three distinct, essential functions in regulating Arp2/3 complex-mediated actin assembly: 1) suppression of spontaneous nucleation by the Arp2/3 complex, which requires proper contacts with p15/ARPC5; 2) propagation of WASp activation signals via contacts with p19/ARPC2; and 3) direct facilitation of actin nucleation through interactions of the extended arm with the VCA domain of WASp."..............
So it appears that Arp2/3 is spontaneous, I am deducting this.
meaning it replicates?
Last Edit: Apr 22, 2010 13:55:59 GMT -5 by skyship
three distinct sites on p40/ARPC1 required for function in vivo: one site contacts p19/ARPC4, one contacts p15/ARPC5, and one site resides in an extended structural “arm” of p40/ARPC1
Seems we have mother and daughter filaments here!
--------------- The structural basis of actin filament branching by the Arp2/3 complex
The actin-related protein 2/3 (Arp2/3) complex mediates the formation of branched actin filaments at the leading edge of motile cells and in the comet tails moving certain intracellular pathogens. Crystal structures of the Arp2/3 complex are available, but the architecture of the junction formed by the Arp2/3 complex at the base of the branch was not known. In this study, we use electron tomography to reconstruct the branch junction with sufficient resolution to show how the Arp2/3 complex interacts with the mother filament. Our analysis reveals conformational changes in both the mother filament and Arp2/3 complex upon branch formation. The Arp2 and Arp3 subunits reorganize into a dimer, providing a short-pitch template for elongation of the daughter filament. Two subunits of the mother filament undergo conformational changes that increase stability of the branch. These data provide a rationale for why branch formation requires cooperative interactions among the Arp2/3 complex, nucleation-promoting factors, an actin monomer, and the mother filament.
Nucelation, meaning changing the nucleus of the cytoskeleton cell Actin monomer? mother filament?
nuclear promoting factor? This is getting closer to the machine itself, it molecular atomic structure.
Turning on the Arp2/3 Complex at Atomic Resolution * Abstract * The recently published 2 Å X-ray crystal structure of bovine Arp2/3 complex gives us atomic scale insight into Arp2/3-mediated actin nucleation, while cryo-EM work and functional studies begin to fill in exciting mechanistic details.
so, it looks like the arp2/3 came from bovine, cow! Is that so we could have the gut of the cow? We could have even more biofilms forming? just like the cow does?
They seemed to get so excited here, hope they did not wet their pants, over this!
more on the nucleus promoting factor:
REGULATION OF ACTIN FILAMENT NETWORK FORMATION THROUGH ARP2/3 COMPLEX: Activation by a Diverse Array of Proteins1
....WASp/Scar family proteins are prominent cellular nucleation promoting factors. They bring together an actin monomer and Arp2/3 complex in solution or on the side of an existing actin filament to initiate a new filament that grows in the barbed end direction. WASp and N-WASP are intrinsically autoinhibited, and their activity is regulated by Rho-family GTPases such as Cdc42, membrane polyphosphoinositides, WIP/verprolin, and SH3 domain proteins. These interactions provide a final common pathway for many signaling inputs to regulate actin polymerization. Microorganisms either activate Arp2/3 complex directly or usurp N-WASP to initiate actin polymerization.
The region of WASP/Scar family proteins that binds and activates the Arp2/3 complex is called a VCA domain and is usually located at the C terminus. A canonical VCA domain is composed of three sequences motifs: one or two V (verprolin homology) sequences (also known as WASP homology 2 or WH2 domains) that bind actin monomers; a C (central or connecting) sequence that is essential for nucleation and has been shown to interact with the Arp2/3 complex; and an A (acidic) sequence that also binds to the Arp2/3 complex and contributes the majority of the binding energy (1) (Fig. 1).
V(verprolin homology) WASP homology 2 or WH2 domains)
==================== verprolin homology WASP homology 2 WH2 domains ==================
Two tandem verprolin homology domains are necessary for a strong activation of Arp2/3 complex-induced actin polymerization and induction of microspike formation by N-WASP
..........."VCA fragments of all of the WASP family proteins: WASP, N-WASP, WAVE1, WAVE2, and WAVE3. All of the VCA fragments stimulated the nucleating activity of Arp2/3 complex. "..........
............."Among them, N-WASP VCA, which possesses two tandem V motifs, had a more potent activity than other VCA proteins. The chimeric protein experiments revealed that the V motif was more important to the activation potency than the CA region; two V motifs were required for full activity of N-WASP. COS7 cells overexpressing N-WASP form microspikes in response to epidermal growth factor."
..."However, when a chimeric protein in which the VCA region of N-WASP is replaced with WAVE1 VCA was overexpressed, microspike formation was suppressed. Interestingly, when the N-WASP VCA region was replaced with WAVE1 VCA, having two V motifs, this chimeric protein could induce microspike formation. These results indicate that strong activation of Arp2/3 complex by N-WASP is mainly caused by its two tandem V motifs, which are essential for actin microspike formation.".............
Two V Motifs in N-WASP VCA Are Required for Its Full Activity
seems we have protein and phospholipid.
SIGNAL TRANSDUCTION: N-WASP Regulation--the Sting in the Tail
Signaling proteins can be regulated by their interactions with other proteins and phospholipids. As Fawcett and Pawson discuss in their Perspective, activation of the N-WASP protein (which coordinates formation of actin filaments) is far more complex, depending on the interaction of N-WASP with both a protein and a phospholipid. The authors explain new results (Prehoda et al.) demonstrating that cooperative binding of the phospholipid PIP2 and the small GTPase Cdc42 to N-WASP results in its activation. The Arp2/3 complex is then able to bind to N-WASP and to proceed with its job of initiating the assembly of actin monomers into actin filaments.
tash: Hi skizit, I have watched all your videos on youtube and cant thank you enough for all you have educated me on. I cry for you alot and a bit for me. I was wanting to send you photos of what is raining down everyday here in Australia in hope you can tell me
Dec 11, 2019 23:28:22 GMT -5
tash: not sure where to send them as hush mail and rocket mail bounced back
Dec 11, 2019 23:30:03 GMT -5