Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2023
Höfundar / Authors: Stefán Ragnar Jónsson (1), Yingxia Hu (2), Yong Xiong (2)
Starfsvettvangur / Affiliations: 1. Keldur Institute for Experimental Pathology, University of Iceland, Reykjavík, Iceland, 2. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA
Kynnir / Presenter: Stefán Ragnar Jónsson
Through evolution organisms have come up with multiple ways to evade lentiviral infections. Among these host proteins is the mammalian APOBEC3 (A3) family of cytidine deaminases that restricts viral infections by mutating viral DNA and impeding reverse transcription. To overcome this antiviral activity, most lentiviruses express a viral accessory protein called Vif, which mediates the ubiquitylation and subsequent proteasomal degradation of A3 proteins. Different lentiviral Vif proteins have evolved to employ the same canonical E3 ubiquitin ligase complexes, along with different non-canonical host co-factors for their activities. Unlike primate lentiviral Vif which recruits CBF-beta as the non-canonical co-factor, non-primate lentiviral Vif proteins have developed differential co-factor recruitment mechanisms. Maedi-visna virus (MVV) sequesters Cyclophilin A (CypA) as the co-factor for the Vif-mediated ubiquitylation of ovine A3 proteins. Here we report a cryo-EM structure of MVV Vif in complex with CypA and E3 ligase components. 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. 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 Vif proteins to capture their cognate host co-factors to evade A3 restrictions.