A computational analysis of the structural determinants of APOBEC3's catalytic activity and vulnerability to HIV-1 Vif.

ABSTRACT: APOBEC3s (A3) are Zn(2+) dependent cytidine deaminases with diverse biological functions and implications for cancer and immunity. Four of the seven human A3s restrict HIV by 'hypermutating' the reverse-transcribed viral genomic DNA. HIV Virion Infectivity Factor (Vif) counters this restriction by targeting A3s to proteasomal degradation. However, there is no apparent correlation between catalytic activity, Vif binding, and sequence similarity between A3 domains. Our comparative structural analysis reveals features required for binding Vif and features influencing polynucleotide deaminase activity in A3 proteins. All Vif-binding A3s share a negatively charged surface region that includes residues previously implicated in binding the highly-positively charged Vif. Additionally, catalyticall

SUBMITTER: Shandilya SM 

PROVIDER: S-EPMC4857191 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature