Structure of SARS coronavirus spike receptor-binding domain complexed with receptor

Science. 2005 Sep 16;309(5742):1864-8. doi: 10.1126/science.1116480.

Abstract

The spike protein (S) of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). A defined receptor-binding domain (RBD) on S mediates this interaction. The crystal structure at 2.9 angstrom resolution of the RBD bound with the peptidase domain of human ACE2 shows that the RBD presents a gently concave surface, which cradles the N-terminal lobe of the peptidase. The atomic details at the interface between the two proteins clarify the importance of residue changes that facilitate efficient cross-species infection and human-to-human transmission. The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Antibodies, Viral / immunology
  • Binding Sites
  • Carboxypeptidases / chemistry*
  • Carboxypeptidases / metabolism
  • Cell Line
  • Crystallography, X-Ray
  • Disease Outbreaks
  • Epitopes
  • Glycosylation
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Membrane Glycoproteins / chemistry*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Peptidyl-Dipeptidase A
  • Protein Conformation
  • Protein Structure, Tertiary
  • Receptors, Virus / chemistry*
  • Receptors, Virus / metabolism
  • SARS Virus / chemistry*
  • SARS Virus / genetics
  • SARS Virus / physiology
  • Severe Acute Respiratory Syndrome / transmission
  • Severe Acute Respiratory Syndrome / virology*
  • Species Specificity
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins / chemistry*
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology
  • Viral Envelope Proteins / metabolism*
  • Viral Vaccines
  • Viverridae / virology

Substances

  • Antibodies, Viral
  • Epitopes
  • Membrane Glycoproteins
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • Viral Vaccines
  • spike glycoprotein, SARS-CoV
  • Carboxypeptidases
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2

Associated data

  • PDB/2AJF