The Flavivirus Precursor Membrane-Envelope Protein Complex: Structure and Maturation

TLDR

Flavivirus maturation converts inert particles into infectious ones via proteolytic cleavage of the precursor membrane protein (prM) during the final assembly stages. The crystal structure of the dengue prM–E heterodimer at 2.2 Å shows the pr peptide beta‑barrel shielding E’s fusion loop, matching cryo‑EM density of immature virus at neutral pH. The structure elucidates the pH‑driven conformational changes that culminate in pr release during budding.

Abstract

Many viruses go through a maturation step in the final stages of assembly before being transmitted to another host. The maturation process of flaviviruses is directed by the proteolytic cleavage of the precursor membrane protein (prM), turning inert virus into infectious particles. We have determined the 2.2 angstrom resolution crystal structure of a recombinant protein in which the dengue virus prM is linked to the envelope glycoprotein E. The structure represents the prM-E heterodimer and fits well into the cryo-electron microscopy density of immature virus at neutral pH. The pr peptide beta-barrel structure covers the fusion loop in E, preventing fusion with host cell membranes. The structure provides a basis for identifying the stages of its pH-directed conformational metamorphosis during maturation, ending with release of pr when budding from the host.