Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor

  title={Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with Receptor},
  author={Fang Li and Wenhui Li and M. Farzan and Stephen C. Harrison},
  pages={1864 - 1868}
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… 

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

High-resolution crystal structures of the receptor-binding domain of the spike protein of SARS-CoV-2 and SARS -CoV in complex with ACE2 provide insights into the binding mode of these coronaviruses and highlight essential ACE2-interacting residues.

Reconstitution of the receptor-binding motif of the SARS coronavirus

The role of the RBM is a bi-functional bioactive surface that can be demonstrated by antibodies such as the neutralizing human anti-SARS monoclonal antibody (mAb) 80R which targets the R BM and competes with the ACE2 receptor for binding.

Interactions Between Sars Coronavirus and its Receptor

The structure of the SARS-CoV RBD reveals in atomic detail the specific and high-affinity interactions between the virus and its receptor and sheds light on critical residue changes that dictate the species specificity of the virus.

Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2

A variant of ACE2 based on deep mutagenesis far outcompetes the natural receptor in binding the SARS-CoV-2 spike protein and gives ACE2 variants with affinities that rival those of monoclonal antibodies.

Critical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor

This work identifies an extended network of salt bridges, hydrophobic and electrostatic interactions, and hydrogen bonding between the receptor-binding domain (RBD) of the S protein and ACE2 and proposes that blocking this site via neutralizing antibody or nanobody could prove an effective strategy to inhibit S-ACE2 interactions.

Featuring ACE2 binding SARS-CoV and SARS-CoV-2 through a conserved evolutionary pattern of amino acid residues

It is speculated that this YGF-based mechanism can act as a protein signature located at the RBM to distinguish coronaviruses able to use angiotensin-converting enzyme 2 as a cell entry receptor.

Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2

Structural comparisons suggested that the SARS-CoV S glycoprotein retains a prefusion architecture after trypsin cleavage into the S1 and S2 subunits and acidic pH treatment, however, binding to the receptor opens up the receptor-binding domain of S1, which could promote the release of the S 1-ACE2 complex and S1 monomers from the prefusion spike and trigger the pre- to postfusion conformational transition.

Prefusion conformation of SARS-CoV-2 receptor-binding domain favours interactions with human receptor ACE2

Cryo-EM structures of SARS-CoV-2 and SARS, caused by Severe Acute Respiratory Syndrome coronavirus, report here that the homotrimer Sars-Cov-2 S receptor-binding domain (RBD) that binds with hACE2 has expanded in size, undergoing a large conformational change relative to SARs- coV-1 S protein.

The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2

Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S, and the mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.



A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2*

It is demonstrated that a 193-amino acid fragment of the S protein bound ACE2 more efficiently than did the full S1 domain (residues 12–672) and a point mutation at aspartic acid 454 abolished association of the fullS1 domain and of the 193-residue fragment with ACE2.

Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus

It is found that a soluble form of ACE2, but not of the related enzyme ACE1, blocked association of the S1 domain with Vero E6 cells, indicating that ACE2 is a functional receptor for SARS-CoV.

Structure of a proteolytically resistant core from the severe acute respiratory syndrome coronavirus S2 fusion protein

The structures presented here can open the path to the design of small-molecule inhibitors of viral entry and candidate vaccine antigens against this virus.

Amino Acids 270 to 510 of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein Are Required for Interaction with Receptor

The construction and expression of a soluble codon-optimized SARS-CoV S glycoprotein comprising the first 1,190 amino acids of the native S glyCoprotein (S1190) is described, indicating that synthetic S Glycoprotein is modified correctly in a mammalian expression system.

Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association.

  • J. SuiWenhui Li W. Marasco
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2004
Data suggest that the 80R human monoclonal antibody may be a useful viral entry inhibitor for the emergency prophylaxis and treatment of SARS, and that the ACE2-binding site of S1 could be an attractive target for subunit vaccine and drug development.

Structural Basis for Coronavirus-mediated Membrane Fusion

The crystal structure of the fusion core of mouse hepatitis virus S protein reveals a central hydrophobic coiled coil trimer surrounded by three helices in an oblique, antiparallel manner, indicating that the structure represents a fusion-active state formed after several conformational changes.

Molecular and Biological Characterization of Human Monoclonal Antibodies Binding to the Spike and Nucleocapsid Proteins of Severe Acute Respiratory Syndrome Coronavirus

Eight human monoclonal antibodies selected from semisynthetic antibody phage display libraries by using whole irradiated severe acute respiratory syndrome (SARS) coronavirus (CoV) virions as target were identified and could be mapped to two SARS-CoV structural proteins: the nucleocapsid (N) and spike (S) proteins.

Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry

It is shown that SARS-CoV shares its receptor ACE2 with HCoV-NL63, which suggests that highly pathogenic variants have ample opportunity to evolve, underlining the need for vaccines against HCoVs.