Maedi–visna virus Vif protein uses motifs distinct from HIV-1 Vif to bind zinc and the cofactor required for A3 degradation
| Autor: | Samantha J. Ziegler, Yingxia Hu, Diana Rubene, Matthew Cook, Stefán R. Jónsson, Kirsten M. Knecht, Yong Xiong |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Visna-maedi virus viruses Cypa medicine.disease_cause Biochemistry Ubiquitin lentivirus vif Gene Products Human Immunodeficiency Virus Cyclophilin Vif virion infectivity factor CypA cyclophilin A Cul5 cullin-5 biology Chemistry zinc virus diseases EloB/C elongin B and elongin C R145D mutation of residue R145 to aspartate Cullin Proteins Ubiquitin ligase Cell biology E3 ubiquitin ligase cyclophilin Cyclophilin A CUL5 Research Article Protein Binding viral protein TCEP tris(2-carboxyethyl)phosphine Viral protein MBP maltose-binding protein CAEV caprine arthritis encephalitis virus Protein–protein interaction 03 medical and health sciences Protein Domains medicine APOBEC3 or A3 apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 Amino Acid Sequence CBFβ core-binding factor subunit beta Molecular Biology FIV feline immunodeficiency virus Cofactor binding 030102 biochemistry & molecular biology protein complex metalloprotein HIV Cell Biology biochemical phenomena metabolism and nutrition biology.organism_classification BIV bovine immunodeficiency virus MVV maedi–visna virus protein–protein interaction 030104 developmental biology Proteolysis biology.protein OaA3Z2-Z3 ovine A3Z2-Z3 |
| Zdroj: | The Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.ra120.015828 |
| Popis: | The mammalian apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3 (APOBEC3 or A3) family of cytidine deaminases restrict viral infections by mutating viral DNA and impeding reverse transcription. To overcome this antiviral activity, most lentiviruses express a viral accessory protein called the virion infectivity factor (Vif), which recruits A3 proteins to cullin-RING E3 ubiquitin ligases such as cullin-5 (Cul5) for ubiquitylation and subsequent proteasomal degradation. Although Vif proteins from primate lentiviruses such as HIV-1 utilize the transcription factor core-binding factor subunit beta as a noncanonical cofactor to stabilize the complex, the maedi-visna virus (MVV) Vif hijacks cyclophilin A (CypA) instead. Because core-binding factor subunit beta 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 topic, we used a combination of in vitro biochemical assays and in vivo 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. |
| Databáze: | OpenAIRE |
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