8e40

From Proteopedia

(Difference between revisions)

Revision as of 05:24, 12 June 2024

Full-length APOBEC3G in complex with HIV-1 Vif, CBF-beta, and fork RNA

Structural highlights

8e40 is a 5 chain structure with sequence from Escherichia coli, Homo sapiens, Human immunodeficiency virus 1 and Macaca mulatta. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.57Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ABC3G_MACMU 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 and simian immunodeficiency viruses (SIVs). 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. May inhibit the mobility of LTR retrotransposons.^[1] ^[2]

Publication Abstract from PubMed

Human APOBEC3G (A3G) is a virus restriction factor that inhibits HIV-1 replication and triggers lethal hypermutation on viral reverse transcripts. HIV-1 viral infectivity factor (Vif) breaches this host A3G immunity by hijacking a cellular E3 ubiquitin ligase complex to target A3G for ubiquitination and degradation. The molecular mechanism of A3G targeting by Vif-E3 ligase is unknown, limiting the antiviral efforts targeting this host-pathogen interaction crucial for HIV-1 infection. Here, we report the cryo-electron microscopy structures of A3G bound to HIV-1 Vif in complex with T cell transcription cofactor CBF-beta and multiple components of the Cullin-5 RING E3 ubiquitin ligase. The structures reveal unexpected RNA-mediated interactions of Vif with A3G primarily through A3G's noncatalytic domain, while A3G's catalytic domain is poised for ubiquitin transfer. These structures elucidate the molecular mechanism by which HIV-1 Vif hijacks the host ubiquitin ligase to specifically target A3G to establish infection and offer structural information for the rational development of antiretroviral therapeutics.

Structural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase.,Ito F, Alvarez-Cabrera AL, Liu S, Yang H, Shiriaeva A, Zhou ZH, Chen XS Sci Adv. 2023 Jan 4;9(1):eade3168. doi: 10.1126/sciadv.ade3168. Epub 2023 Jan 4. PMID:36598981^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Mariani R, Chen D, Schrofelbauer B, Navarro F, Konig R, Bollman B, Munk C, Nymark-McMahon H, Landau NR. Species-specific exclusion of APOBEC3G from HIV-1 virions by Vif. Cell. 2003 Jul 11;114(1):21-31. PMID:12859895
↑ Hultquist JF, Lengyel JA, Refsland EW, LaRue RS, Lackey L, Brown WL, Harris RS. Human and rhesus APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H demonstrate a conserved capacity to restrict Vif-deficient HIV-1. J Virol. 2011 Nov;85(21):11220-34. doi: 10.1128/JVI.05238-11. Epub 2011 Aug 10. PMID:21835787 doi:10.1128/JVI.05238-11
↑ Ito F, Alvarez-Cabrera AL, Liu S, Yang H, Shiriaeva A, Zhou ZH, Chen XS. Structural basis for HIV-1 antagonism of host APOBEC3G via Cullin E3 ligase. Sci Adv. 2023 Jan 4;9(1):eade3168. doi: 10.1126/sciadv.ade3168. Epub 2023 Jan 4. PMID:36598981 doi:http://dx.doi.org/10.1126/sciadv.ade3168

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/8e40"

@@ Line 4: / Line 4: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[8e40]] is a 5 chain structure with sequence from [https://en.wikipedia.org/wiki/Escherichia_coli Escherichia coli], [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/Macaca_mulatta Macaca mulatta]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E40 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E40 FirstGlance]. <br>
-</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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.57&#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=8e40 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e40 OCA], [https://pdbe.org/8e40 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e40 RCSB], [https://www.ebi.ac.uk/pdbsum/8e40 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e40 ProSAT]</span></td></tr>
 </table>
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 8e40" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Virion infectivity factor|Virion infectivity factor]]
 == References ==
 <references/>

8e40

From Proteopedia

Revision as of 05:24, 12 June 2024

Full-length APOBEC3G in complex with HIV-1 Vif, CBF-beta, and fork RNA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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