Functional domain organization of human APOBEC3G.

@article{citeulike:3036846, 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.}, address = {Department of Molecular Genetics and Microbiology, Center for Virology, Box 3025, Duke University Medical Center, Durham, NC 27710, USA.}, author = {Gooch, Barry D D. and Cullen, Bryan R R. }, citeulike-article-id = {3036846}, doi = {http://dx.doi.org/10.1016/j.virol.2008.06.013}, issn = {0042-6822}, journal = {Virology}, keywords = {apobec}, month = {July}, posted-at = {2008-07-23 14:09:01}, priority = {2}, title = {Functional domain organization of human APOBEC3G.}, url = {http://dx.doi.org/10.1016/j.virol.2008.06.013}, year = {2008} }

TY - JOUR ID - citeulike:3036846 L3 - citeulike-article-id:3036846 TI - Functional domain organization of human APOBEC3G. JF - Virology AD - Department of Molecular Genetics and Microbiology, Center for Virology, Box 3025, Duke University Medical Center, Durham, NC 27710, USA. SN - 0042-6822 N2 - 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. KW - apobec AU - Gooch, Barry D AU - Cullen, Bryan R PY - 2008/07/17/ UR - http://dx.doi.org/10.1016/j.virol.2008.06.013 ER -