Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors

Autor: Wentao Li, Alexandra C. Walls, M. Alejandra Tortorici, Z. Wang, Maximilian M. Sauer, Young-Jun Park, Frank DiMaio, David Veesler, Berend Jan Bosch
Přispěvatelé: Department of Biochemistry [Washington ], University of Washington [Seattle], Utrecht University [Utrecht], Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Research reported in this publication was supported by the National Institute of General Medical Sciences (R01GM120553, D.V.), the National Institute of Allergy and Infectious Diseases (HHSN272201700059C, D.V.), a Pew Biomedical Scholars Award (D.V.), an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund (D.V.) and a Swiss National Science Foundation PostDoc Mobility fellowship (M.M.S.). M.A.T. acknowledges support from the Institut Pasteur. This work was also supported by the Arnold and Mabel Beckman cryo-EM center at the University of Washington, dI&I I&I-1, LS Virologie, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Viral membrane fusion
Models
Molecular
Protein Conformation
viruses
[SDV]Life Sciences [q-bio]
MESH: Spike Glycoprotein
Coronavirus
Plasma protein binding
medicine.disease_cause
chemistry.chemical_compound
0302 clinical medicine
Protein structure
MESH: Structure-Activity Relationship
MESH: Protein Conformation
Structural Biology
Models
Neuraminic acid
Protein Interaction Mapping
Carbohydrate Conformation
Viral
MESH: Carbohydrate Conformation
Receptor
chemistry.chemical_classification
0303 health sciences
Middle East Respiratory Syndrome Coronavirus/chemistry
Spike Glycoprotein
3. Good health
Cell biology
Coronavirus/chemistry
Spike Glycoprotein
Coronavirus
Middle East Respiratory Syndrome Coronavirus
MESH: Protein Domains
MESH: Cryoelectron Microscopy
MESH: Models
Molecular
Protein Binding
Viral protein
Dipeptidyl Peptidase 4
Coronacrisis-Taverne
MESH: Sialic Acids
Article
03 medical and health sciences
Structure-Activity Relationship
Sialic Acids/chemistry
Protein Domains
Viral entry
MESH: Hemagglutination
Viral
medicine
Humans
MESH: Protein Binding
Binding site
Molecular Biology
Hemagglutination
Viral
030304 developmental biology
Spike Glycoprotein
Coronavirus/chemistry
Binding Sites
MESH: Humans
Hemagglutination
Dipeptidyl Peptidase 4/chemistry
Cryoelectron Microscopy
MESH: Protein Interaction Mapping
MESH: Middle East Respiratory Syndrome Coronavirus
Molecular
MESH: Dipeptidyl Peptidase 4
chemistry
MESH: Binding Sites
Sialic Acids
Glycoprotein
030217 neurology & neurosurgery
Zdroj: Nature Structural and Molecular Biology
Nature Structural and Molecular Biology, Nature Publishing Group, 2019, 26 (12), pp.1151-1157. ⟨10.1038/s41594-019-0334-7⟩
Nature Structural and Molecular Biology, 26(12), 1151. Nature Publishing Group
Nature Structural and Molecular Biology, 2019, 26 (12), pp.1151-1157. ⟨10.1038/s41594-019-0334-7⟩
Nature Structural & Molecular Biology
ISSN: 1545-9993
1545-9985
DOI: 10.1038/s41594-019-0334-7⟩
Popis: The Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and often lethal respiratory illness in humans, and no vaccines or specific treatments are available. Infections are initiated via binding of the MERS-CoV spike (S) glycoprotein to sialosides and dipeptidyl-peptidase 4 (the attachment and entry receptors, respectively). To understand MERS-CoV engagement of sialylated receptors, we determined the cryo-EM structures of S in complex with 5-N-acetyl neuraminic acid, 5-N-glycolyl neuraminic acid, sialyl-LewisX, α2,3-sialyl-N-acetyl-lactosamine and α2,6-sialyl-N-acetyl-lactosamine at 2.7–3.0 Å resolution. We show that recognition occurs via a conserved groove that is essential for MERS-CoV S-mediated attachment to sialosides and entry into human airway epithelial cells. Our data illuminate MERS-CoV S sialoside specificity and suggest that selectivity for α2,3-linked over α2,6-linked receptors results from enhanced interactions with the former class of oligosaccharides. This study provides a structural framework explaining MERS-CoV attachment to sialoside receptors and identifies a site of potential vulnerability to inhibitors of viral entry.
Cryo-EM structures of MERS-CoV S glycoprotein trimer in complex with different sialosides reveal how the virus engages with sialylated receptors, providing insight into receptor specificity and selectivity.
Databáze: OpenAIRE
Externí odkaz: