6c3r
From Proteopedia
Cricket paralysis virus RNAi suppressor protein CrPV-1A
Structural highlights
FunctionPOLN_CRPVC Protein 1A functions as a suppressor of RNA-mediated gene silencing, an antiviral defense mechanism of insect cells. Inhibits siRNA function, but does not interfere with miRNA pathway. Does not bind to dsRNA or siRNA.[1] RNA-directed RNA polymerase replicates genomic and antigenomic RNA.[PROSITE-ProRule:PRU00539][2] Publication Abstract from PubMedThe 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. A Viral Protein Restricts Drosophila RNAi Immunity by Regulating Argonaute Activity and Stability.,Nayak A, Kim DY, Trnka MJ, Kerr CH, Lidsky PV, Stanley DJ, Rivera BM, Li KH, Burlingame AL, Jan E, Frydman J, Gross JD, Andino R Cell Host Microbe. 2018 Oct 10;24(4):542-557.e9. doi: 10.1016/j.chom.2018.09.006. PMID:30308158[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||
