4r4h: Difference between revisions
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==Crystal structure of non-neutralizing, A32-like antibody 2.2c in complex with HIV-1 Env gp120== | ==Crystal structure of non-neutralizing, A32-like antibody 2.2c in complex with HIV-1 Env gp120== | ||
<StructureSection load='4r4h' size='340' side='right' caption='[[4r4h]], [[Resolution|resolution]] 4.28Å' scene=''> | <StructureSection load='4r4h' size='340' side='right'caption='[[4r4h]], [[Resolution|resolution]] 4.28Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4r4h]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R4H OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4r4h]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4R4H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4R4H FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 4.28Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4r4h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4r4h OCA], [https://pdbe.org/4r4h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4r4h RCSB], [https://www.ebi.ac.uk/pdbsum/4r4h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4r4h ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/ENV_HV1B9 ENV_HV1B9] Oligomerizes in the host endoplasmic reticulum into predominantly trimers. In a second time, gp160 transits in the host Golgi, where glycosylation is completed. The precursor is then proteolytically cleaved in the trans-Golgi and thereby activated by cellular furin or furin-like proteases to produce gp120 and gp41.[HAMAP-Rule:MF_04083] Attaches the virus to the host lymphoid cell by binding to the primary receptor CD4. This interaction induces a structural rearrangement creating a high affinity binding site for a chemokine coreceptor like CXCR4 and/or CCR5. Acts as a ligand for CD209/DC-SIGN and CLEC4M/DC-SIGNR, which are respectively found on dendritic cells (DCs), and on endothelial cells of liver sinusoids and lymph node sinuses. These interactions allow capture of viral particles at mucosal surfaces by these cells and subsequent transmission to permissive cells. HIV subverts the migration properties of dendritic cells to gain access to CD4+ T-cells in lymph nodes. Virus transmission to permissive T-cells occurs either in trans (without DCs infection, through viral capture and transmission), or in cis (following DCs productive infection, through the usual CD4-gp120 interaction), thereby inducing a robust infection. In trans infection, bound virions remain infectious over days and it is proposed that they are not degraded, but protected in non-lysosomal acidic organelles within the DCs close to the cell membrane thus contributing to the viral infectious potential during DCs' migration from the periphery to the lymphoid tissues. On arrival at lymphoid tissues, intact virions recycle back to DCs' cell surface allowing virus transmission to CD4+ T-cells.[HAMAP-Rule:MF_04083] 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 fusion of viral and target intracellular membranes, 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. Complete fusion occurs in host cell endosomes and is dynamin-dependent, however some lipid transfer might occur at the plasma membrane. The virus undergoes clathrin-dependent internalization long before endosomal fusion, thus minimizing the surface exposure of conserved viral epitopes during fusion and reducing the efficacy of inhibitors targeting these epitopes. Membranes fusion leads to delivery of the nucleocapsid into the cytoplasm.[HAMAP-Rule:MF_04083] | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 4r4h" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Antibody 3D structures|Antibody 3D structures]] | |||
*[[Gp120 3D structures|Gp120 3D structures]] | |||
*[[3D structures of human antibody|3D structures of human antibody]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Homo sapiens]] | ||
[[Category: | [[Category: Human immunodeficiency virus 1]] | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Acharya P]] | ||
[[Category: | [[Category: Huang C-C]] | ||
[[Category: | [[Category: Kwong PD]] | ||
[[Category: Mclellan J]] | |||