A fold switch regulates conformation of an alphavirus RNA-dependent RNA polymerase.

ABSTRACT: Alphaviruses are mosquito-vectored, positive-strand RNA viruses causing rheumatic and neurological diseases. Like all RNA viruses, they encode an RNA-dependent RNA polymerase (RdRp, nsP4). Purification of an nsP4 derivative capable of processive RNA synthesis from a heteropolymeric template has been unsuccessful. Prior studies indicated O'nyong-nyong virus (ONNV) nsP4 is soluble and requires additional nonstructural proteins for activity. We performed biochemical and biophysical characterization of ONNV nsP4, including analytical ultracentrifugation and small-angle X-ray scattering (SAXS), revealing an extended conformation inconsistent with AlphaFold predictions of a compact structure. Fold switching was required for the extended conformation. Hydrogen-deuterium exchange mass spectrometry

SUBMITTER: Arnold JJ 

PROVIDER: S-EPMC12817075 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature