View source for 8cx2


==Cryo-EM structure of human APOBEC3G/HIV-1 Vif/CBFbeta/ELOB/ELOC dimeric complex in State 2==
<StructureSection load='8cx2' size='340' side='right'caption='[[8cx2]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8cx2]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens], [https://en.wikipedia.org/wiki/Human_immunodeficiency_virus_1 Human immunodeficiency virus 1] and [https://en.wikipedia.org/wiki/Spodoptera_frugiperda Spodoptera frugiperda]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8CX2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8CX2 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=8cx2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8cx2 OCA], [https://pdbe.org/8cx2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8cx2 RCSB], [https://www.ebi.ac.uk/pdbsum/8cx2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8cx2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/ABC3G_HUMAN ABC3G_HUMAN] DNA deaminase (cytidine deaminase) that mediates a form of innate resistance to retroviral infections (at least to HIV-1 infection) by triggering G-to-A hypermutation in the newly synthesized viral DNA. The replacements C-to-U in the minus strand DNA of HIV-1 during reverse transcription, leads to G-to-A transitions in the plus strand. The inhibition of viral replication is either due to the degradation of the minus strand before its integration or to the lethality of the hypermutations. Modification of both DNA strands is not excluded. This antiviral activity is neutralized by the virion infectivity factor (VIF), that prevents the incorporation of APOBEC3G into progeny HIV-1 virions by both inhibiting its translation and/or by inducing its ubiquitination and subsequent degradation by the 26S proteasome. May also prevent the transposition of a subset of retroelements. Binds a variety of RNAs, but does not display detectable APOB, NF1 and NAT1 mRNA editing.<ref>PMID:14557625</ref> <ref>PMID:12167863</ref> <ref>PMID:12808466</ref> <ref>PMID:12809610</ref> <ref>PMID:12808465</ref> <ref>PMID:12859895</ref> <ref>PMID:12970355</ref> <ref>PMID:14528300</ref> <ref>PMID:15031497</ref> <ref>PMID:16527742</ref> <ref>PMID:21123384</ref> <ref>PMID:18288108</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The APOBEC3 (A3) proteins are host antiviral cellular proteins that hypermutate the viral genome of diverse viral families. In retroviruses, this process requires A3 packaging into viral particles(1-4). The lentiviruses encode a protein, Vif, that antagonizes A3 family members by targeting them for degradation. Diversification of A3 allows host escape from Vif whereas adaptations in Vif enable cross-species transmission of primate lentiviruses. How this 'molecular arms race' plays out at the structural level is unknown. Here, we report the cryogenic electron microscopy structure of human APOBEC3G (A3G) bound to HIV-1 Vif, and the hijacked cellular proteins that promote ubiquitin-mediated proteolysis. A small surface explains the molecular arms race, including a cross-species transmission event that led to the birth of HIV-1. Unexpectedly, we find that RNA is a molecular glue for the Vif-A3G interaction, enabling Vif to repress A3G by ubiquitin-dependent and -independent mechanisms. Our results suggest a model in which Vif antagonizes A3G by intercepting it in its most dangerous form for the virus-when bound to RNA and on the pathway to packaging-to prevent viral restriction. By engaging essential surfaces required for restriction, Vif exploits a vulnerability in A3G, suggesting a general mechanism by which RNA binding helps to position key residues necessary for viral antagonism of a host antiviral gene.

The structural basis for HIV-1 Vif antagonism of human APOBEC3G.,Li YL, Langley CA, Azumaya CM, Echeverria I, Chesarino NM, Emerman M, Cheng Y, Gross JD Nature. 2023 Mar;615(7953):728-733. doi: 10.1038/s41586-023-05779-1. Epub 2023 , Feb 8. PMID:36754086<ref>PMID:36754086</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8cx2" style="background-color:#fffaf0;"></div>

==See Also==
*[[Virion infectivity factor|Virion infectivity factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Spodoptera frugiperda]]
[[Category: Azumaya CM]]
[[Category: Cheng Y]]
[[Category: Chesarino NM]]
[[Category: Echeverria I]]
[[Category: Emerman M]]
[[Category: Gross JD]]
[[Category: Langley C]]
[[Category: Li Y]]