Model structure of APOBEC3C reveals a binding pocket modulating ribonucleic acid interaction required for encapsidation

被引：37

作者：

Stauch, Benjamin ^{[2
]}

Hofmann, Henning ^{[3
]}

Perkovic, Mario ^{[3
]}

Weisel, Martin ^{[2
]}

Kopietz, Ferdinand ^{[3
]}

Cichutek, Klaus ^{[3
]}

Muenk, Carsten ^{[1
]}

Schneider, Gisbert ^{[2
]}

机构：

[1] Univ Dusseldorf, Clin Gastroenterol Hepatol & Infectiol, D-40225 Dusseldorf, Germany

[2] Goethe Univ Frankfurt, D-60323 Frankfurt, Germany

[3] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2009年 / 106卷 / 29期

关键词：

Bioinformatics; immunodeficiency; protein structure; protein-protein interaction; retrovirus; CRYSTAL-STRUCTURE; ENZYME APOBEC3G; PROTEIN; VIRUS; DNA; DOMAIN; HYPERMUTATION; RESTRICTION; DYNAMICS; VIRION;

D O I：

10.1073/pnas.0900979106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Human APOBEC3 (A3) proteins form part of the intrinsic immunity to retroviruses. Carrying 1 or 2 copies of a cytidine deaminase motif, A3s act by deamination of retroviral genomes during reverse transcription. HIV-1 overcomes this inhibition by the Vif protein, which prevents incorporation of A3 into virions. In this study we modeled and probed the structure of APOBEC3C (A3C), a single-domain A3 with strong antilentiviral activity. The 3-dimensional protein model was used to predict the effect of mutations on antiviral activity, which was tested in a Delta vif simian immunodeficiency virus (SIV) reporter virus assay. We found that A3C activity requires protein dimerization for antiviral activity against SIV. Furthermore, by using a structure-based algorithm for automated pocket extraction, we detected a putative substrate binding pocket of A3C distal from the zinc-coordinating deaminase motif. Mutations in this region diminished antiviral activity by excluding A3C from virions. We found evidence that the small 5.8S RNA specifically binds to this locus and mediates incorporation of A3C into virus particles.

引用

页码：12079 / 12084

页数：6

共 49 条

[31] Adaptive evolution and antiviral activity of the conserved mammalian cytidine deaminase APOBEC3H [J].