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

Young-Jun Park; Alexandra C Walls; Zhaoqian Wang; Maximillian M Sauer; Wentao Li; M Alejandra Tortorici; Berend-Jan Bosch; Frank DiMaio; David Veesler

doi:10.1038/s41594-019-0334-7

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

Young-Jun Park
, Alexandra C Walls
, Zhaoqian Wang
, Maximillian M Sauer
, Wentao Li
, M Alejandra Tortorici
, Berend-Jan Bosch
, Frank DiMaio
, David Veesler

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1151-1157
Number of pages	7
Journal	Nature Structural and Molecular Biology
Volume	26
Issue number	12
DOIs	https://doi.org/10.1038/s41594-019-0334-7
Publication status	Published - Dec 2019

Keywords

Binding Sites
Carbohydrate Conformation
Cryoelectron Microscopy
Dipeptidyl Peptidase 4/chemistry
Hemagglutination, Viral
Humans
Middle East Respiratory Syndrome Coronavirus/chemistry
Models, Molecular
Protein Binding
Protein Conformation
Protein Domains
Protein Interaction Mapping
Sialic Acids/chemistry
Spike Glycoprotein, Coronavirus/chemistry
Structure-Activity Relationship

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors",

abstract = "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 {\AA} 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.",

keywords = "Binding Sites, Carbohydrate Conformation, Cryoelectron Microscopy, Dipeptidyl Peptidase 4/chemistry, Hemagglutination, Viral, Humans, Middle East Respiratory Syndrome Coronavirus/chemistry, Models, Molecular, Protein Binding, Protein Conformation, Protein Domains, Protein Interaction Mapping, Sialic Acids/chemistry, Spike Glycoprotein, Coronavirus/chemistry, Structure-Activity Relationship",

author = "Young-Jun Park and Walls, \{Alexandra C\} and Zhaoqian Wang and Sauer, \{Maximillian M\} and Wentao Li and Tortorici, \{M Alejandra\} and Berend-Jan Bosch and Frank DiMaio and David Veesler",

year = "2019",

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doi = "10.1038/s41594-019-0334-7",

language = "English",

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journal = "Nature Structural and Molecular Biology",

issn = "1545-9993",

publisher = "Nature Research",

number = "12",

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T1 - Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors

AU - Park, Young-Jun

AU - Walls, Alexandra C

AU - Wang, Zhaoqian

AU - Sauer, Maximillian M

AU - Li, Wentao

AU - Tortorici, M Alejandra

AU - Bosch, Berend-Jan

AU - DiMaio, Frank

AU - Veesler, David

PY - 2019/12

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N2 - 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.

AB - 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.

KW - Binding Sites

KW - Carbohydrate Conformation

KW - Cryoelectron Microscopy

KW - Dipeptidyl Peptidase 4/chemistry

KW - Hemagglutination, Viral

KW - Humans

KW - Middle East Respiratory Syndrome Coronavirus/chemistry

KW - Models, Molecular

KW - Protein Binding

KW - Protein Conformation

KW - Protein Domains

KW - Protein Interaction Mapping

KW - Sialic Acids/chemistry

KW - Spike Glycoprotein, Coronavirus/chemistry

KW - Structure-Activity Relationship

U2 - 10.1038/s41594-019-0334-7

DO - 10.1038/s41594-019-0334-7

M3 - Article

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VL - 26

SP - 1151

EP - 1157

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

IS - 12

ER -

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

Abstract

Keywords

UN SDGs

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