biostudies-literatureJiang XNational Natural Foundation of China1907https://www.ebi.ac.uk/biostudies/studies/S-EPMC9504981biostudies-literatureUnknown14(9)Positive-sense single-stranded RNA viruses replicate in virus-induced membranous organelles for maximum efficiency and immune escaping. The replication of potato virus X (PVX) takes place on the endoplasmic reticulum (ER); however, how PVX-encoded RNA-dependent RNA polymerase (RdRp) is associated with the ER is still unknown. A proline-kinked amphipathic α-helix was recently found in the MET domain of RdRp. In this study, we further illustrate that the first α-helix of the MET domain is also required for ER association. Moreover, we found that the MET domain forms multimers on ER and the first α-helix is essential for multimerization. These results suggest that the RdRp of PVX adopts more than one hydrophobic motif for membrane association and for multimerization.VirusesThe N-Terminal α-Helix of Potato Virus X-Encoded RNA-Dependent RNA Polymerase Is Required for Membrane Association and Multimerization.PMC950498132022071Luan YChai MLi YYang YJiang XWang YDeng WCheng XWu XfalseThe N-Terminal α-Helix of Potato Virus X-Encoded RNA-Dependent RNA Polymerase Is Required for Membrane Association and Multimerization.Positive-sense single-stranded RNA viruses replicate in virus-induced membranous organelles for maximum efficiency and immune escaping. The replication of potato virus X (PVX) takes place on the endoplasmic reticulum (ER); however, how PVX-encoded RNA-dependent RNA polymerase (RdRp) is associated with the ER is still unknown. A proline-kinked amphipathic α-helix was recently found in the MET domain of RdRp. In this study, we further illustrate that the first α-helix of the MET domain is also required for ER association. Moreover, we found that the MET domain forms multimers on ER and the first α-helix is essential for multimerization. These results suggest that the RdRp of PVX adopts more than one hydrophobic motif for membrane association and for multimerization.2022-01-01T00:00:00Z2022 Aug2025-04-04T09:29:55.962Z2025-04-04T09:29:55.962ZS-EPMC95049813614671410.3390/v14091907