6Q07

MERS-CoV S structure in complex with 2,6-sialyl-N-acetyl-lactosamine

Summary for 6Q07

• Entry DOI: 10.2210/pdb6q07/pdb
• EMDB information: 20542 20543 20544 20545 20829
• Related PRD ID: PRD_900046
• Descriptor: Spike glycoprotein, alpha-D-mannopyranose-(1-3)-beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• Functional Keywords: coronavirus, spike glycoprotein, mers-cov, membrane fusion, structural genomics, seattle structural genomics center for infectious disease, ssgcid, viral protein
• Biological source: Human betacoronavirus 2c EMC/2012
• Total number of polymer chains: 3
• Total formula weight: 474928.34

Authors

Park, Y.J.,Walls, A.C.,Wang, Z.,Sauer, M.,Li, W.,Tortorici, M.A.,Bosch, B.J.,DiMaio, F.D.,Veesler, D.,Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2019-08-01, release date: 2019-12-11, Last modification date: 2024-10-23)

Primary citation

Park, Y.J.,Walls, A.C.,Wang, Z.,Sauer, M.M.,Li, W.,Tortorici, M.A.,Bosch, B.J.,DiMaio, F.,Veesler, D.
Structures of MERS-CoV spike glycoprotein in complex with sialoside attachment receptors.
Nat.Struct.Mol.Biol., 26:1151-1157, 2019

PubMed 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-Lewis, 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.

PubMed: 31792450
DOI: 10.1038/s41594-019-0334-7

Experimental method

ELECTRON MICROSCOPY (2.9 Å)