Functional domain organization of human APOBEC3G.
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.
Gooch
Barry D
BD
Department of Molecular Genetics and Microbiology, Center for Virology, Box 3025, Duke University Medical Center, Durham, NC 27710, USA. barry.gooch@duke.edu
Cullen
Bryan R
BR
D000071480:APOBEC-3G Deaminase; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism*; D015497:HIV-1 / Q000276:immunology* / Q000502:physiology*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D019065:Virus Assembly; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000378:metabolism
D054301:gag Gene Products, Human Immunodeficiency Virus; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase