Serveur d'exploration MERS

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

Identifieur interne : 000009 ( France/Analysis ); précédent : 000008; suivant : 000010

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

Auteurs : Young-Jun Park [États-Unis] ; Alexandra C. Walls [États-Unis] ; Zhaoqian Wang [États-Unis] ; Maximillian M. Sauer [États-Unis] ; Wentao Li [Pays-Bas] ; M. Alejandra Tortorici [États-Unis, France] ; Berend-Jan Bosch [Pays-Bas] ; Frank Dimaio [États-Unis] ; David Veesler [États-Unis]

Source :

RBID : PMC:7097669

Descripteurs français

English descriptors

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.


Url:
DOI: 10.1038/s41594-019-0334-7
PubMed: 31792450
PubMed Central: 7097669


Affiliations:


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PMC:7097669

Le document en format XML

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<term>Binding Sites</term>
<term>Carbohydrate Conformation</term>
<term>Cryoelectron Microscopy</term>
<term>Dipeptidyl Peptidase 4 (chemistry)</term>
<term>Dipeptidyl Peptidase 4 (metabolism)</term>
<term>Dipeptidyl Peptidase 4 (ultrastructure)</term>
<term>Hemagglutination, Viral</term>
<term>Humans</term>
<term>Middle East Respiratory Syndrome Coronavirus (chemistry)</term>
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<term>Protein Binding</term>
<term>Protein Conformation</term>
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<term>Conformation des glucides</term>
<term>Conformation des protéines</term>
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<term>Dipeptidyl peptidase 4 (ultrastructure)</term>
<term>Domaines protéiques</term>
<term>Glycoprotéine de spicule des coronavirus ()</term>
<term>Glycoprotéine de spicule des coronavirus (métabolisme)</term>
<term>Glycoprotéine de spicule des coronavirus (ultrastructure)</term>
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<term>Carbohydrate Conformation</term>
<term>Cryoelectron Microscopy</term>
<term>Hemagglutination, Viral</term>
<term>Humans</term>
<term>Models, Molecular</term>
<term>Protein Binding</term>
<term>Protein Conformation</term>
<term>Protein Domains</term>
<term>Protein Interaction Mapping</term>
<term>Structure-Activity Relationship</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr">
<term>Acides sialiques</term>
<term>Cartographie d'interactions entre protéines</term>
<term>Conformation des glucides</term>
<term>Conformation des protéines</term>
<term>Coronavirus du syndrome respiratoire du Moyen-Orient</term>
<term>Cryomicroscopie électronique</term>
<term>Dipeptidyl peptidase 4</term>
<term>Domaines protéiques</term>
<term>Glycoprotéine de spicule des coronavirus</term>
<term>Humains</term>
<term>Hémagglutination virale</term>
<term>Liaison aux protéines</term>
<term>Modèles moléculaires</term>
<term>Relation structure-activité</term>
<term>Sites de fixation</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front>
<div type="abstract" xml:lang="en">
<p id="Par1">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-
<italic>N</italic>
-acetyl neuraminic acid, 5-
<italic>N</italic>
-glycolyl neuraminic acid, sialyl-Lewis
<sup>X</sup>
, α2,3-sialyl-
<italic>N</italic>
-acetyl-lactosamine and α2,6-sialyl-
<italic>N</italic>
-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.</p>
</div>
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<affiliations>
<list>
<country>
<li>France</li>
<li>Pays-Bas</li>
<li>États-Unis</li>
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<region>
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<region name="Washington (État)">
<name sortKey="Park, Young Jun" sort="Park, Young Jun" uniqKey="Park Y" first="Young-Jun" last="Park">Young-Jun Park</name>
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<name sortKey="Wang, Zhaoqian" sort="Wang, Zhaoqian" uniqKey="Wang Z" first="Zhaoqian" last="Wang">Zhaoqian Wang</name>
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<country name="France">
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</affiliations>
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