Evolution and activation mechanism of the flavivirus class II membrane-fusion machinery.

ABSTRACT: The flavivirus envelope glycoproteins prM and E drive the assembly of icosahedral, spiky immature particles that bud across the membrane of the endoplasmic reticulum. Maturation into infectious virions in the trans-Golgi network involves an acid-pH-driven rearrangement into smooth particles made of (prM/E)₂ dimers exposing a furin site for prM cleavage into "pr" and "M". Here we show that the prM "pr" moiety derives from an HSP40 cellular chaperonin. Furthermore, the X-ray structure of the tick-borne encephalitis virus (pr/E)₂ dimer at acidic pH reveals the E 150-loop as a hinged-lid that opens at low pH to expose a positively-charged pr-binding pocket at the E dimer interface, inducing (prM/E)₂ dimer formation to generate smooth particles in the Golgi. Fur

SUBMITTER: Vaney MC 

PROVIDER: S-EPMC9239988 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature