Insight into the HIV-1 Vif SOCS-box -ElonginBC interaction

1. Summary The HIV-1 viral infectivity factor (Vif) neutralizes cell-encoded antiviral APOBEC3 proteins by recruiting a cellular ElonginB (EloB)/ElonginC (EloC)/ Cullin5-containing ubiquitin ligase complex, resulting in APOBEC3 ubiquitination and proteolysis. The suppressors-of-cytokine-signalling-like domain (SOCS-box) of HIV-1 Vif is essential for E3 ligase engagement, and contains a BC box as well as an unusual proline-rich motif. Here, we report the NMR solution structure of the Vif SOCS–ElonginBC (EloBC) complex. In contrast to SOCS-boxes described in other proteins, the HIV-1 Vif SOCS-box contains only one a-helical domain followed by a b-sheet fold. The SOCS-box of Vif binds primarily to EloC by hydrophobic interactions. The functionally essential prolinerich motif mediates a direct but weak interaction with residues 101–104 of EloB, inducing a conformational change from an unstructured state to a structured state.Thestructureofthecomplexandbiophysicalstudiesprovidedetailedinsight into the function of Vif’s proline-rich motif and reveal novel dynamic information on the Vif–EloBC interaction.