Höfundar:
Stefán Ragnar Jónsson, Yingxia Hu, Yong Xiong
Introduction: Lentiviruses express Vif molecules to overcome host restrictions by targeting the antiviral APOBEC3 proteins for destruction in cellular ubiquitin-proteasome pathways. Different lentiviral Vifs have evolved to employ the same canonical E3 ubiquitin ligase complexes, along with different non-canonical host cofactors for their activities. Unlike primate lentiviral Vif which recruits CBFβ as the noncanonical cofactor, non-primate lentiviral Vif proteins have developed differential cofactor recruitment mechanisms. Maedi–visna virus (MVV) sequesters CypA as the noncanonical cofactor for the Vif-mediated ubiquitination of ovine APOBEC3 proteins. Here we report a cryo-EM structure of MVV Vif in complex with CypA and E3 ligase components.
Methods: A complex of MVV Vif, Elongin B/C and CyPA was used to obtain an image of the structure using Cryo-EM. Biochemical assays and A3 degradation assays were used to study novel motifs required for the binding of MVV Vif to the cofactor CypA
Results: Our work reveals conserved and novel structural features of MVV Vif, and the molecular mechanism by which it interacts with the E3 ligase components and CypA.
Conclusions: The results highlight the important similarities and differences between MVV and primate lentiviral Vif proteins, advancing our understanding of the molecular determinants that help drive the evolution of lentiviral Vifs to capture their cognate host cofactors to evade APOBEC3 restrictions.