Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state

J Biol Chem. 2006 Apr 28;281(17):11965-71. doi: 10.1074/jbc.M601174200. Epub 2006 Feb 28.

Abstract

The envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (SARS-CoV) is known to mediate viral entry. Similar to other class 1 viral fusion proteins, the heptad repeat regions of SARS-CoV spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. Recently, the structure of a post-fusion form of SARS-CoV spike, which consists of isolated domains of heptad repeats 1 and 2 (HR1 and HR2), has been determined by x-ray crystallography. To date there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2. In this work we present the NMR structure of the HR2 domain (residues 1141-1193) from SARS-CoV (termed S2-HR2) in the presence of the co-solvent trifluoroethanol. We find that in the absence of HR1, S2-HR2 forms a coiled coil symmetric trimer with a complex molecular mass of 18 kDa. The S2-HR2 structure, which is the first example of the prefusion form of coronavirus envelope, supports the current model of viral membrane fusion and gives insight into the design of structure-based antagonists of SARS.

MeSH terms

  • Crystallography, X-Ray
  • Hemagglutinins, Viral
  • Humans
  • Membrane Glycoproteins / chemical synthesis*
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism
  • Models, Molecular*
  • Protein Conformation
  • Repetitive Sequences, Amino Acid* / genetics
  • Severe acute respiratory syndrome-related coronavirus / chemistry*
  • Severe acute respiratory syndrome-related coronavirus / genetics
  • Severe acute respiratory syndrome-related coronavirus / metabolism
  • Solubility
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / metabolism
  • Viral Fusion Proteins / chemical synthesis*
  • Viral Fusion Proteins / genetics
  • Viral Fusion Proteins / metabolism

Substances

  • Hemagglutinins, Viral
  • Membrane Glycoproteins
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • Viral Fusion Proteins

Associated data

  • PDB/2FXP