Identification of the HIV-1 Vif and Human APOBEC3G Protein Interface

Michael Letko, Thijs Booiman, Neeltje Kootstra, Viviana Simon, Marcel Ooms

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


Human cells express natural antiviral proteins, such as APOBEC3G (A3G), that potently restrict HIV replication. As a counter-defense, HIV encodes the accessory protein Vif, which binds A3G and mediates its proteasomal degradation. Our structural knowledge on how Vif and A3G interact is limited, because a co-structure is not available. We identified specific points of contact between Vif and A3G by using functional assays with full-length A3G, patient-derived Vif variants, and HIV forced evolution. These anchor points were used to model and validate the Vif-A3G interface. The resultant co-structure model shows that the negatively charged β4-α4 A3G loop, which contains primate-specific variation, is the core Vif binding site and forms extensive interactions with a positively charged pocket in HIV Vif. Our data present a functional map of this viral-host interface and open avenues for targeted approaches to block HIV replication by obstructing the Vif-A3G interaction.

Original languageEnglish
Pages (from-to)1789-1799
Number of pages11
JournalCell Reports
Issue number9
StatePublished - 1 Dec 2015


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