Functional domain organization of human APOBEC3G.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Gooch, BD; Cullen, BR

Published Date

  • September 15, 2008

Published In

Volume / Issue

  • 379 / 1

Start / End Page

  • 118 - 124

PubMed ID

  • 18639915

Pubmed Central ID

  • PMC2601658

Electronic International Standard Serial Number (EISSN)

  • 1096-0341

Digital Object Identifier (DOI)

  • 10.1016/j.virol.2008.06.013


  • eng

Conference Location

  • United States