Líffræðifélag Íslands - biologia.is
Líffræðiráðstefnan 2021
Erindi/veggspjald / Talk/poster E83
Höfundar / Authors: Stefán Ragnar Jónsson (1), Diana Rubene (1), Ragna Brá Guðnadóttir (1), Kirsten Knecht (2), Yong Xiong (2)
Starfsvettvangur / Affiliations: 1. Tilraunastöð HÍ í meinafræði að Keldum, 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 defenses is the mammalian APOBEC3 (A3) family of cytidine deaminases that restricts 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. While primate lentiviral Vif proteins utilize the transcription factor CBFβ as a cofactor to stabilize the complex, maedi-visna (MVV) Vif hijacks cyclophillin A (CypA) instead. Since CBFβ and CypA are both highly conserved among mammals, the requirement for two different cellular cofactors suggests that these two A3-targeting Vif proteins have different biochemical and structural properties. To investigate this, we used a combination of biochemical assays and A3 degradation assays to study motifs required for the MVV Vif to bind zinc ion, Cul5, and the cofactor CypA. Our results demonstrate that although some common motifs between the HIV-1 Vif and MVV Vif are involved in recruiting Cul5, different determinants in the MVV Vif are required for cofactor binding and stabilization of the E3 ligase complex, such as the zinc-binding motif and N- and C-terminal regions of the protein. Results from this study advance our understanding of the mechanism of MVV Vif recruitment of cellular factors and the evolution of lentiviral Vif proteins.