View source for 7rpu


==Crystal Structure of Protective Human Antibody 3A6 Fab Against Ebola Virus with GP Stalk/MPER Epitope Peptide==
<StructureSection load='7rpu' size='340' side='right'caption='[[7rpu]], [[Resolution|resolution]] 1.27&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7rpu]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Ebola_virus_-_Eckron_(Zaire,_1976) Ebola virus - Eckron (Zaire, 1976)] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RPU OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RPU FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.27&#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=7rpu FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7rpu OCA], [https://pdbe.org/7rpu PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7rpu RCSB], [https://www.ebi.ac.uk/pdbsum/7rpu PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7rpu ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/VGP_EBOEC VGP_EBOEC] Trimeric GP1,2 complexes form the virion surface spikes and mediate the viral entry processes, with GP1 acting as the receptor-binding subunit and GP2 as the membrane fusion subunit. At later times of infection, down-regulates the expression of various host cell surface molecules that are essential for immune surveillance and cell adhesion. Down-modulates several integrins including ITGA1, ITGA2, ITGA3, ITGA4, ITGA5, ITGA6, ITGAV and ITGB1. This decrease in cell adhesion molecules may lead to cell detachment, contributing to the disruption of blood vessel integrity and hemorrhages developed during infection (cytotoxicity). Interacts with host TLR4 and thereby stimulates the differentiation and activation of monocytes leading to bystander death of T-lymphocytes. Down-regulates as well the function of host natural killer cells. Counteracts the antiviral effect of host BST2/tetherin that restricts release of progeny virions from infected cells. However, cooperates with VP40 and host BST2 to activate canonical NF-kappa-B pathway in a manner dependent on neddylation.[UniProtKB:Q05320]  Functions as a decoy for anti-GP1,2 antibodies thereby contributing to viral immune evasion. Interacts and activates host macrophages and dendritic cells inducing up-regulation of cytokine transcription. This effect is mediated throught activation of host TLR4.[UniProtKB:Q05320]  Responsible for binding to the receptor(s) on target cells. Interacts with CD209/DC-SIGN and CLEC4M/DC-SIGNR which act as cofactors for virus entry into dendritic cells (DCs) and endothelial cells (By similarity). Binding to the macrophage specific lectin CLEC10A also seems to enhance virus infectivity (By similarity). Interaction with FOLR1/folate receptor alpha may be a cofactor for virus entry in some cell types, although results are contradictory (By similarity). Members of the Tyro3 receptor tyrosine kinase family also seem to be cell entry factors in filovirus infection (By similarity). Once attached, the virions are internalized through clathrin-dependent endocytosis and/or macropinocytosis. After internalization of the virus into the endosomes of the host cell, proteolysis of GP1 by two cysteine proteases, CTSB/cathepsin B and CTSL/cathepsin L removes the glycan cap and allows GP1 binding to the host entry receptor NPC1. NPC1-binding, Ca(2+) and acidic pH induce a conformational change of GP2, which unmasks its fusion peptide and permit membranes fusion (By similarity).[UniProtKB:O11457][UniProtKB:Q05320][UniProtKB:Q66814]  Acts as a class I viral fusion protein. Under the current model, the protein has at least 3 conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes. Responsible for penetration of the virus into the cell cytoplasm by mediating the fusion of the membrane of the endocytosed virus particle with the endosomal membrane. Low pH in endosomes induces an irreversible conformational change in GP2, releasing the fusion hydrophobic peptide.[UniProtKB:Q05320]

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Ahmed R]]
[[Category: Davis CW]]
[[Category: Salie ZL]]
[[Category: Saphire EO]]