View source for 3j0c


==Models of E1, E2 and CP of Venezuelan Equine Encephalitis Virus TC-83 strain restrained by a near atomic resolution cryo-EM map==
<SX load='3j0c' size='340' side='right' viewer='molstar' caption='[[3j0c]], [[Resolution|resolution]] 4.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3j0c]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Venezuelan_equine_encephalitis_virus_(strain_TC-83) Venezuelan equine encephalitis virus (strain TC-83)]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3J0C OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3J0C FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4.8&#8491;</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3j0c FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3j0c OCA], [https://pdbe.org/3j0c PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3j0c RCSB], [https://www.ebi.ac.uk/pdbsum/3j0c PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3j0c ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/POLS_EEVV8 POLS_EEVV8] Capsid protein possesses a protease activity that results in its autocatalytic cleavage from the nascent structural protein. Following its self-cleavage, the capsid protein transiently associates with ribosomes, and within several minutes the protein binds to viral RNA and rapidly assembles into icosaedric core particles. The resulting nucleocapsid eventually associates with the cytoplasmic domain of E2 at the cell membrane, leading to budding and formation of mature virions. New virions attach to target cells, and after clathrin-mediated endocytosis their membrane fuses with the host endosomal membrane. This leads to the release of the nucleocapsid into the cytoplasm, followed by an uncoating event necessary for the genomic RNA to become accessible. The uncoating might be triggered by the interaction of capsid proteins with ribosomes. Binding of ribosomes would release the genomic RNA since the same region is genomic RNA-binding and ribosome-binding (By similarity).  E3 protein's function is unknown (By similarity).  E2 is responsible for viral attachment to target host cell, by binding to the cell receptor. Synthesized as a p62 precursor which is processed by furin at the cell membrane just before virion budding, giving rise to E2-E1 heterodimer. The p62-E1 heterodimer is stable, whereas E2-E1 is unstable and dissociate at low pH. p62 is processed at the last step, presumably to avoid E1 fusion activation before its final export to cell surface. E2 C-terminus contains a transitory transmembrane that would be disrupted by palmitoylation, resulting in reorientation of the C-terminal tail from lumenal to cytoplasmic side. This step is critical since E2 C-terminus is involved in budding by interacting with capsid proteins. This release of E2 C-terminus in cytoplasm occurs lately in protein export, and precludes premature assembly of particles at the endoplasmic reticulum membrane (By similarity).  6K is a constitutive membrane protein involved in virus glycoprotein processing, cell permeabilization, and the budding of viral particles. Disrupts the calcium homeostasis of the cell, probably at the endoplasmic reticulum level. This leads to cytoplasmic calcium elevation. Because of its lipophilic properties, the 6K protein is postulated to influence the selection of lipids that interact with the transmembrane domains of the glycoproteins, which, in turn, affects the deformability of the bilayer required for the extreme curvature that occurs as budding proceeds. Present in low amount in virions, about 3% compared to viral glycoproteins (By similarity).  E1 is a class II viral fusion protein. Fusion activity is inactive as long as E1 is bound to E2 in mature virion. After virus attachment to target cell and endocytosis, acidification of the endosome would induce dissociation of E1/E2 heterodimer and concomitant trimerization of the E1 subunits. This E1 trimer is fusion active, and promotes release of viral nucleocapsid in cytoplasm after endosome and viral membrane fusion. Efficient fusion requires the presence of cholesterol and sphingolipid in the target membrane (By similarity).
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Venezuelan equine encephalitis virus (VEEV), a member of the membrane-containing Alphavirus genus, is a human and equine pathogen, and has been developed as a biological weapon. Using electron cryo-microscopy (cryo-EM), we determined the structure of an attenuated vaccine strain, TC-83, of VEEV to 4.4 A resolution. Our density map clearly resolves regions (including E1, E2 transmembrane helices and cytoplasmic tails) that were missing in the crystal structures of domains of alphavirus subunits. These new features are implicated in the fusion, assembly and budding processes of alphaviruses. Furthermore, our map reveals the unexpected E3 protein, which is cleaved and generally thought to be absent in the mature VEEV. Our structural results suggest a mechanism for the initial stage of nucleocapsid core formation, and shed light on the virulence attenuation, host recognition and neutralizing activities of VEEV and other alphavirus pathogens.

4.4 A cryo-EM structure of an enveloped alphavirus Venezuelan equine encephalitis virus.,Zhang R, Hryc CF, Cong Y, Liu X, Jakana J, Gorchakov R, Baker ML, Weaver SC, Chiu W EMBO J. 2011 Aug 9. doi: 10.1038/emboj.2011.261. PMID:21829169<ref>PMID:21829169</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3j0c" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virus coat proteins 3D structures|Virus coat proteins 3D structures]]
== References ==
<references/>
__TOC__
</SX>
[[Category: Large Structures]]
[[Category: Baker ML]]
[[Category: Chiu W]]
[[Category: Cong Y]]
[[Category: Gorchakov R]]
[[Category: Hryc CF]]
[[Category: Jakana J]]
[[Category: Liu X]]
[[Category: Weaver SC]]
[[Category: Zhang R]]