| Autor: |
Michael Letko, Thijs Booiman, Neeltje Kootstra, Viviana Simon, Marcel Ooms |
| Jazyk: |
angličtina |
| Rok vydání: |
2015 |
| Předmět: |
|
| Zdroj: |
Cell Reports, Vol 13, Iss 9, Pp 1789-1799 (2015) |
| Druh dokumentu: |
article |
| ISSN: |
2211-1247 |
| DOI: |
10.1016/j.celrep.2015.10.068 |
| Popis: |
Human cells express natural antiviral proteins, such as APOBEC3G (A3G), that potently restrict HIV replication. As a counter-defense, HIV encodes the accessory protein Vif, which binds A3G and mediates its proteasomal degradation. Our structural knowledge on how Vif and A3G interact is limited, because a co-structure is not available. We identified specific points of contact between Vif and A3G by using functional assays with full-length A3G, patient-derived Vif variants, and HIV forced evolution. These anchor points were used to model and validate the Vif-A3G interface. The resultant co-structure model shows that the negatively charged β4-α4 A3G loop, which contains primate-specific variation, is the core Vif binding site and forms extensive interactions with a positively charged pocket in HIV Vif. Our data present a functional map of this viral-host interface and open avenues for targeted approaches to block HIV replication by obstructing the Vif-A3G interaction. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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