The N-Terminal α-Helix of Potato Virus X-Encoded RNA-Dependent RNA Polymerase Is Required for Membrane Association and Multimerization

Abstract

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.

DREAMM: a web-based server for drugging protein-membrane interfaces as a novel workflow for targeted drug design

“…The protein-membrane interface prediction function of DREAMM has been thoroughly tested as described in Refs. ( Chatzigoulas and Cournia, 2022; Jiang et al , 2022 ; Valenstein et al ., 2022 ). Moreover, DREAMM was assessed on four recently crystallized conformations of the protein FakB1, whose W180 is an important amino acid for FakB1-membrane binding ( Gullett et al , 2022 ).…”