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

Science. 2008 Mar 28;319(5871):1830-4. doi: 10.1126/science.1153263.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Crystallography, X-Ray
  • Dengue Virus / chemistry*
  • Dengue Virus / growth & development
  • Dimerization
  • Hydrogen-Ion Concentration
  • Models, Molecular
  • Protein Conformation
  • Protein Precursors / chemistry
  • Protein Precursors / metabolism
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / metabolism
  • Viral Matrix Proteins / chemistry*
  • Viral Matrix Proteins / metabolism
  • Virus Assembly

Substances

  • E-glycoprotein, Dengue virus type 2
  • Protein Precursors
  • Recombinant Fusion Proteins
  • Viral Envelope Proteins
  • Viral Matrix Proteins

Associated data

  • PDB/3C5X
  • PDB/3C6E