Cryo-EM structures of MERS-CoV and SARS-CoV spike glycoproteins reveal the dynamic receptor binding domains

By Yuan Yuan, D. Cao, Yanfang Zhang, Jun Ma, Jianxun Qi, Qihui Wang, Guangwen Lu, Ying Wu, Jinghua Yan, Yi Shi and 2 more. Nature Communications, 2017

738 citations recorded by the source corpus.

The envelope spike (S) proteins of MERS-CoV and SARS-CoV determine the virus host tropism and entry into host cells, and constitute a promising target for the development of prophylactics and therapeutics. Here, we present high-resolution structures of the trimeric MERS-CoV and SARS-CoV S proteins in its pre-fusion conformation by single particle cryo-electron microscopy. The overall structures resemble that from other coronaviruses including HKU1, MHV and NL63 reported recently, with the exception of the receptor binding domain (RBD). We captured two states of the RBD with receptor binding region either buried (lying state) or exposed (standing state), demonstrating an inherently flexible RBD readily recognized by the receptor. Further sequence conservation analysis of six human-infecting coronaviruses revealed that the fusion peptide, HR1 region and the central helix are potential targets for eliciting broadly neutralizing antibodies. Host tropism and cell entry of pathogenic coronaviruses are mediated by their envelope spike (S) proteins. Here the authors present structural analyses of trimeric MERS-CoV and SARS-CoV S proteins in pre-fusion conformation, and reveal two states of the receptor binding domain that suggest new avenues for the generation of neutralizing antibodies.

Subfields: Animal Science and Zoology, Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/5de87684bf85758756337f7a03806489efd6c764

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

1. D. Veesler
2. Fang Li
3. A. Walls
4. M. A. Tortorici
5. J. Shang
6. Yushun Wan
7. A. Tortoricia
8. David Veeslera

In Infectious Diseases

1. D. Veesler
2. A. Walls
3. M. A. Tortorici
4. Fang Li
5. J. Shang
6. Yushun Wan
7. Q. Geng
8. Ian A. Wilson

Citations in the corpus

• Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, neutral): “…(Song et al., 2018; Walls et al., 2019), the cryo-EM observation of S 1 subunit trimers released from the MERS-CoV S ectodomain upon cleavage at S 1 /S 2 (Yuan et al., 2017) and the fact that S spontaneously re-folds to the postfusion state in the absence of the S 1 subunit (Walls et al., 2017).”
• Coronavirus disease 2019 (COVID-19): current status and future perspectives (2020, background): “The spike surface glycoprotein plays a key role in its attachment to host cells and can be further cleaved by host proteases into an N-terminal S1 subunit and a membrane-bound C-terminal S2 region [17] .”
• Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein (2020, background): “Similarly to SARS-CoV S and MERS-CoV S (Gui et al., 2017; Kirchdoerfer et al., 2018; Pallesen et al., 2017; Song et al., 2018; Walls et al., 2019; Yuan et al., 2017) , we found that the SARS-CoV-2 S trimer exists in multiple, distinct conformational states resulting from S B opening at the trimer ap”
• Controlling the SARS-CoV-2 spike glycoprotein conformation (2020, neutral): “These include SARS-CoV-2 1,3 , SARS 4–8 , MERS 4,9 , and other human 1,10 and murine 11 β -CoV spike proteins.”
• Cryo-EM Structure of the 2019-nCoV Spike in the Prefusion Conformation (2020, background): “state, which is thought to be less stable (10-13).”
• Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry (2019, background): “present in two different states – standing up and lying down (18, 21) (Fig.”
• Unexpected Receptor Functional Mimicry Elucidates Activation of Coronavirus Fusion (2020, positive): “Based on these findings, it was hypothesized that receptor binding may initiate membrane fusion (Gui et al., 2017; Pallesen et al., 2017; Yuan et al., 2017).”
• 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;”
• Origin and evolution of pathogenic coronaviruses (2018, neutral): “Electron microscopic studies have shown that the SARS-CoV S protein forms a clover shaped trimer, with three S1 heads and a trimeric S2 stalk 74,75 .”