View source for 8fvi


==Human APOBEC3H bound to HIV-1 Vif in complex with CBF-beta, ELOB, ELOC, and CUL5==
<StructureSection load='8fvi' size='340' side='right'caption='[[8fvi]], [[Resolution|resolution]] 3.24&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8fvi]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [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=8FVI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8FVI 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]] 3.24&#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=8fvi FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8fvi OCA], [https://pdbe.org/8fvi PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8fvi RCSB], [https://www.ebi.ac.uk/pdbsum/8fvi PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8fvi ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/PEBB_HUMAN PEBB_HUMAN] Note=A chromosomal aberration involving CBFB is associated with acute myeloid leukemia of M4EO subtype. Pericentric inversion inv(16)(p13;q22). The inversion produces a fusion protein that consists of the 165 N-terminal residues of CBF-beta (PEPB2) with the tail region of MYH11.
== Function ==
[https://www.uniprot.org/uniprot/PEBB_HUMAN PEBB_HUMAN] CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters. CBFB enhances DNA binding by RUNX1.
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== Publication Abstract from PubMed ==
Human APOBEC3 (A3) cytidine deaminases are antiviral factors that are particularly potent against retroviruses. As a countermeasure, HIV-1 uses a viral infectivity factor (Vif) to target specific human A3s for proteasomal degradation. Vif recruits cellular transcription cofactor CBF-beta and Cullin-5 (CUL5) RING E3 ubiquitin ligase to bind different A3s distinctively, but how this is accomplished remains unclear in the absence of the atomic structure of the complex. Here, we present the cryo-EM structures of HIV-1 Vif in complex with human A3H, CBF-beta and components of CUL5 ubiquitin ligase (CUL5, ELOB, and ELOC). Vif nucleates the entire complex by directly binding four human proteins, A3H, CBF-beta, CUL5, and ELOC. The structures reveal a large interface area between A3H and Vif, primarily mediated by an alpha-helical side of A3H and a five-stranded beta-sheet of Vif. This A3H-Vif interface unveils the basis for sensitivity-modulating polymorphism of both proteins, including a previously reported gain-of-function mutation in Vif isolated from HIV/AIDS patients. Our structural and functional results provide insights into the remarkable interplay between HIV and humans and would inform development efforts for anti-HIV therapeutics.

Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H.,Ito F, Alvarez-Cabrera AL, Kim K, Zhou ZH, Chen XS Nat Commun. 2023 Aug 28;14(1):5241. doi: 10.1038/s41467-023-40955-x. PMID:37640699<ref>PMID:37640699</ref>

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

==See Also==
*[[Virion infectivity factor|Virion infectivity factor]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Escherichia coli]]
[[Category: Homo sapiens]]
[[Category: Human immunodeficiency virus 1]]
[[Category: Large Structures]]
[[Category: Alvarez-Cabrera AL]]
[[Category: Chen XS]]
[[Category: Ito F]]
[[Category: Zhou ZH]]