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Virology. 2008 Sep 15;379(1):118-24. doi: 10.1016/j.virol.2008.06.013. Epub 2008 Jul 18.

Functional domain organization of human APOBEC3G.

Author information

1
Department of Molecular Genetics and Microbiology, Center for Virology, Box 3025, Duke University Medical Center, Durham, NC 27710, USA. barry.gooch@duke.edu

Abstract

Human APOBEC3 proteins exist in two forms containing either a single cytidine deaminase domain (CDA) or two CDAs. Strikingly, the proteins that are capable of effectively inhibiting the infectivity of Vif-deficient HIV-1 (HIV-1DeltaVif), such as APOBEC3G (A3G), contain two CDAs. In contrast, single-domain APOBEC3 proteins such as APOBEC3A (A3A) are weak inhibitors of HIV-1DeltaVif, even though A3A is an active cytidine deaminase and a potent inhibitor of retrotransposon mobility. Here, we demonstrate that the ability to bind to Gag and package into HIV-1 virions is entirely contained within the amino-terminal half of A3G. By changing three adjacent amino acids in A3A, to the sequence found in the N-terminal half of A3G, we were able to confer on A3A the ability to be efficiently incorporated into HIV-1 virions and to bind HIV-1 Gag. Nevertheless, this A3A mutant remained a weak inhibitor of HIV-1 infectivity, suggesting that segregation of the Gag-binding/virion incorporation and cytidine deaminase/virus-inhibition activities of APOBEC3 proteins into two tandem CDA regions promotes the efficient inhibition of retrovirus infectivity by APOBEC3 proteins.

PMID:
18639915
PMCID:
PMC2601658
DOI:
10.1016/j.virol.2008.06.013
[Indexed for MEDLINE]
Free PMC Article

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