6C3R
Cricket paralysis virus RNAi suppressor protein CrPV-1A
Summary for 6C3R
| Entry DOI | 10.2210/pdb6c3r/pdb |
| Descriptor | Cricket paralysis virus 1A protein (2 entities in total) |
| Functional Keywords | rnai inhibitor, viral protein |
| Biological source | Cricket paralysis virus (isolate Teleogryllus commodus/Australia/CrPVVIC/1968) |
| Total number of polymer chains | 2 |
| Total formula weight | 33583.90 |
| Authors | Nayak, A.,Kim, D.Y.,Andino, R.,Gross, J. (deposition date: 2018-01-10, release date: 2018-10-17, Last modification date: 2024-10-30) |
| Primary citation | Nayak, A.,Kim, D.Y.,Trnka, M.J.,Kerr, C.H.,Lidsky, P.V.,Stanley, D.J.,Rivera, B.M.,Li, K.H.,Burlingame, A.L.,Jan, E.,Frydman, J.,Gross, J.D.,Andino, R. A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability. Cell Host Microbe, 24:542-557.e9, 2018 Cited by PubMed Abstract: The dicistrovirus, Cricket paralysis virus (CrPV) encodes an RNA interference (RNAi) suppressor, 1A, which modulates viral virulence. Using the Drosophila model, we combined structural, biochemical, and virological approaches to elucidate the strategies by which CrPV-1A restricts RNAi immunity. The atomic resolution structure of CrPV-1A uncovered a flexible loop that interacts with Argonaute 2 (Ago-2), thereby inhibiting Ago-2 endonuclease-dependent immunity. Mutations disrupting Ago-2 binding attenuates viral pathogenesis in wild-type but not Ago-2-deficient flies. CrPV-1A also contains a BC-box motif that enables the virus to hijack a host Cul2-Rbx1-EloBC ubiquitin ligase complex, which promotes Ago-2 degradation and virus replication. Our study uncovers a viral-based dual regulatory program that restricts antiviral immunity by direct interaction with and modulation of host proteins. While the direct inhibition of Ago-2 activity provides an efficient mechanism to establish infection, the recruitment of a ubiquitin ligase complex enables CrPV-1A to amplify Ago-2 inactivation to restrict further antiviral RNAi immunity. PubMed: 30308158DOI: 10.1016/j.chom.2018.09.006 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.6 Å) |
Structure validation
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