Cryo-electron microscopy structure of a coronavirus spike glycoprotein trimer

By A. Walls, M. A. Tortorici, B. Bosch, Brandon Frenz, P. Rottier, Frank DiMaio, F. Rey, D. Veesler. 2016

534 citations recorded by the source corpus.

The tremendous pandemic potential of coronaviruses was demonstrated twice in the past few decades by two global outbreaks of deadly pneumonia. Entry of coronaviruses into cells is mediated by the transmembrane spike glycoprotein S, which forms a trimer carrying receptor-binding and membrane fusion functions. S also contains the principal antigenic determinants and is the target of neutralizing antibodies. Here we present the structure of a mouse coronavirus S trimer ectodomain determined at 4.0 Å resolution by single particle cryo-electron microscopy. It reveals the metastable pre-fusion architecture of S and highlights key interactions stabilizing it. The structure shares a common core with paramyxovirus F proteins, implicating mechanistic similarities and an evolutionary connection between these viral fusion proteins. The accessibility of the highly conserved fusion peptide at the periphery of the trimer indicates potential vaccinology strategies to elicit broadly neutralizing antibodies against coronaviruses. Finally, comparison with crystal structures of human coronavirus S domains allows rationalization of the molecular basis for species specificity based on the use of spatially contiguous but distinct domains.

Subfields: Animal Science and Zoology, Epidemiology, Infectious Diseases

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Animal Science and Zoology

In Epidemiology

In Infectious Diseases

Citations in the corpus

Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 (2020, positive): “Similar to other coronaviruses, SARS-CoV-2 entry into host cells is mediated by the transmembrane spike (S) glycoprotein, which forms prominent homotrimers protruding from the viral surface (Tortorici and Veesler, 2019; Walls et al., 2016a; Walls et al., 2017).”
Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, unknown): “…SARS-CoV-2 entry into host cells is mediated by the transmembrane spike (S) glycoprotein, which forms prominent homotrimers protruding from the viral surface (Ke et al., 2020; Tortorici and Veesler, 2019; Turo (cid:1) nova´ al., 2020; Walls et al., 2016a; 2017). of nAbs against SARS-CoV-2.”
Immunogenicity and structures of a rationally designed prefusion MERS-CoV spike antigen (2017, background): “In the structures of the S proteins from MHV and HCoV-HKU1 all three RBDs were shown to be in a tightly packed, closed configuration (17, 18).”
Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (2020, methodology): “…a prefusion stabilized ectodomain trimer construct with an abrogated furin S1/S2 cleavage site (Tortorici et al., 2019; Walls et al., 2017a; Walls et al., 2016a; Walls et al., 2019), two consecutive proline stabilizing mutations (Kirchdoerfer et al., 2018; Pallesen et al., 2017), and a…”
Structural insights into coronavirus entry (2019, background): “In the prefusion S conformation, a central helix stretches along the threefold axis, perpendicular to the viral membrane, and is located downstream the HR1 motif, which folds as four consecutive α-helices (Kirchdoerfer et al., 2016; Walls et al., 2016a) .”
Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion (2020, unknown): “, 2004), the high sequence conservation of this region among coronavirus S glycoproteins (Walls et al., 2016a), and the identification of a neutralization epitope within a comparable breach of the HIV-1 Env glycan shield (McCoy et al.”
The human coronavirus HCoV-229E S-protein structure and receptor binding (2019, background): “The S-protein is a trimer in both the pre-fusion and post-fusion conformations and cryo-EM analysis has provided structures for both conformations (Kirchdoerfer et al., 2016; Walls et al., 2016a; Kirchdoerfer et al., 2018; Walls et al., 2016b; Walls et al., 2017; Gui et al., 2017; Yuan et al., 2017;”
Controlling the SARS-CoV-2 spike glycoprotein conformation (2020, unknown): “The wealth of structural information for β -CoV spike proteins, including the recently determined cryo-EM structures of the SARS-CoV-2 spike 1–11 , has provided a rich source of detailed geometric information from which to begin precise examination of the macromolecular transitions underlying…”