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4j4j

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{{STRUCTURE_4j4j| PDB=4j4j | SCENE= }}
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==Crystal structure of the APOBEC3F Vif binding domain==
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===Crystal structure of the APOBEC3F Vif binding domain===
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<StructureSection load='4j4j' size='340' side='right' caption='[[4j4j]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
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{{ABSTRACT_PUBMED_24185281}}
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4j4j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J4J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4J4J FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">APOBEC3F ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Cytidine_deaminase Cytidine deaminase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.4.5 3.5.4.5] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4j4j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4j4j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4j4j RCSB], [http://www.ebi.ac.uk/pdbsum/4j4j PDBsum]</span></td></tr>
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</table>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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The human APOBEC3 family of DNA cytosine deaminases serves as a front-line intrinsic immune response to inhibit the replication of diverse retroviruses. APOBEC3F and APOBEC3G are the most potent factors against HIV-1. As a countermeasure, HIV-1 viral infectivity factor (Vif) targets APOBEC3s for proteasomal degradation. Here we report the crystal structure of the Vif-binding domain in APOBEC3F and a novel assay to assess Vif-APOBEC3 binding. Our results point to an amphipathic surface that is conserved in APOBEC3s as critical for Vif susceptibility in APOBEC3F. Electrostatic interactions likely mediate Vif binding. Moreover, structure-guided mutagenesis reveals a straight ssDNA-binding groove distinct from the Vif-binding site, and an 'aromatic switch' is proposed to explain DNA substrate specificities across the APOBEC3 family. This study opens new lines of inquiry that will further our understanding of APOBEC3-mediated retroviral restriction and provides an accurate template for structure-guided development of inhibitors targeting the APOBEC3-Vif axis.
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==Function==
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Structural determinants of HIV-1 Vif susceptibility and DNA binding in APOBEC3F.,Siu KK, Sultana A, Azimi FC, Lee JE Nat Commun. 2013 Nov 4;4:2593. doi: 10.1038/ncomms3593. PMID:24185281<ref>PMID:24185281</ref>
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[[http://www.uniprot.org/uniprot/ABC3F_HUMAN ABC3F_HUMAN]] DNA deaminase (cytidine deaminase) which acts as an inhibitor of retrovirus replication and retrotransposon mobility via deaminase-dependent and -independent mechanisms. Exhibits antiviral activity against vif-deficient HIV-1. After the penetration of retroviral nucleocapsids into target cells of infection and the initiation of reverse transcription, it can induce the conversion of cytosine to uracil in the minus-sense single-strand viral DNA, leading to G-to-A hypermutations in the subsequent plus-strand viral DNA. The resultant detrimental levels of mutations in the proviral genome, along with a deamination-independent mechanism that works prior to the proviral integration, together exert efficient antiretroviral effects in infected target cells. Selectively targets single-stranded DNA and does not deaminate double-stranded DNA or single- or double-stranded RNA. Exhibits antiviral activity also against hepatitis B virus (HBV), equine infectious anemia virus (EIAV), xenotropic MuLV-related virus (XMRV) and simian foamy virus (SFV) and may inhibit the mobility of LTR and non-LTR retrotransposons. May also play a role in the epigenetic regulation of gene expression through the process of active DNA demethylation.<ref>PMID:15152192</ref> <ref>PMID:16527742</ref> <ref>PMID:16378963</ref> <ref>PMID:19458006</ref> <ref>PMID:20219927</ref> <ref>PMID:20335265</ref> <ref>PMID:20062055</ref> <ref>PMID:21496894</ref> <ref>PMID:21835787</ref> <ref>PMID:22915799</ref> <ref>PMID:22807680</ref> <ref>PMID:23097438</ref> <ref>PMID:23152537</ref>
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[4j4j]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4J4J OCA].
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</div>
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:024185281</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Cytidine deaminase]]
[[Category: Cytidine deaminase]]
[[Category: Human]]
[[Category: Human]]
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[[Category: Lee, J E.]]
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[[Category: Lee, J E]]
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[[Category: Siu, K K.]]
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[[Category: Siu, K K]]
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[[Category: Sultana, A.]]
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[[Category: Sultana, A]]
[[Category: Alpha/beta]]
[[Category: Alpha/beta]]
[[Category: Hydrolase]]
[[Category: Hydrolase]]

Revision as of 12:57, 21 December 2014

Crystal structure of the APOBEC3F Vif binding domain

4j4j, resolution 3.10Å

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