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.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Park YJ,Walls AC,Wang Z,Sauer MM,Li W,Tortorici MA,Bosch BJ,DiMaio F,Veesler Ddoi
10.1038/s41594-019-0334-7subject
Has Abstractpub_date
2019-12-01 00:00:00pages
1151-1157issue
12eissn
1545-9993issn
1545-9985pii
10.1038/s41594-019-0334-7journal_volume
26pub_type
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