Crystal structure of the prefusion surface glycoprotein of the prototypic arenavirus LCMV

Nat Struct Mol Biol. 2016 Jun;23(6):513-521. doi: 10.1038/nsmb.3210. Epub 2016 Apr 25.

Abstract

Arenaviruses exist worldwide and can cause hemorrhagic fever and neurologic disease. A single glycoprotein expressed on the viral surface mediates entry into target cells. This glycoprotein, termed GPC, contains a membrane-associated signal peptide, a receptor-binding subunit termed GP1 and a fusion-mediating subunit termed GP2. Although GPC is a critical target of antibodies and vaccines, the structure of the metastable GP1-GP2 prefusion complex has remained elusive for all arenaviruses. Here we describe the crystal structure of the fully glycosylated prefusion GP1-GP2 complex of the prototypic arenavirus LCMV at 3.5 Å. This structure reveals the conformational changes that the arenavirus glycoprotein must undergo to cause fusion and illustrates the fusion regions and potential oligomeric states.

Publication types

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

MeSH terms

  • Animals
  • Cell Line
  • Crystallography, X-Ray
  • Drosophila
  • Glycosylation
  • Humans
  • Lymphocytic Choriomeningitis / metabolism
  • Lymphocytic Choriomeningitis / virology
  • Lymphocytic choriomeningitis virus / chemistry*
  • Lymphocytic choriomeningitis virus / physiology
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / metabolism
  • Models, Molecular
  • Protein Conformation
  • Protein Multimerization
  • Protein Sorting Signals
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / metabolism
  • Virus Internalization

Substances

  • Membrane Glycoproteins
  • Protein Sorting Signals
  • Protein Subunits
  • Viral Envelope Proteins