Sialoglycan binding triggers spike opening in a human coronavirus

Matti F. Pronker, Robert Creutznacher, Ieva Drulyte, Ruben J. G. Hulswit, Zeshi Li, Frank J. M. Kuppeveld, Joost Snijder, Yifei Lang, Berend-Jan Bosch, Geert-Jan Boons, Martin Frank, Raoul J. Groot () and Daniel L. Hurdiss ()
Additional contact information
Matti F. Pronker: Utrecht University
Robert Creutznacher: Utrecht University
Ieva Drulyte: Thermo Fisher Scientific
Ruben J. G. Hulswit: Utrecht University
Zeshi Li: Utrecht University
Frank J. M. Kuppeveld: Utrecht University
Joost Snijder: Utrecht University
Yifei Lang: Utrecht University
Berend-Jan Bosch: Utrecht University
Geert-Jan Boons: Utrecht University
Martin Frank: Biognos AB
Raoul J. Groot: Utrecht University
Daniel L. Hurdiss: Utrecht University

Nature, 2023, vol. 624, issue 7990, 201-206

Abstract: Abstract Coronavirus spike proteins mediate receptor binding and membrane fusion, making them prime targets for neutralizing antibodies. In the cases of severe acute respiratory syndrome coronavirus, severe acute respiratory syndrome coronavirus 2 and Middle East respiratory syndrome coronavirus, spike proteins transition freely between open and closed conformations to balance host cell attachment and immune evasion1–5. Spike opening exposes domain S1B, allowing it to bind to proteinaceous receptors6,7, and is also thought to enable protein refolding during membrane fusion4,5. However, with a single exception, the pre-fusion spike proteins of all other coronaviruses studied so far have been observed exclusively in the closed state. This raises the possibility of regulation, with spike proteins more commonly transitioning to open states in response to specific cues, rather than spontaneously. Here, using cryogenic electron microscopy and molecular dynamics simulations, we show that the spike protein of the common cold human coronavirus HKU1 undergoes local and long-range conformational changes after binding a sialoglycan-based primary receptor to domain S1A. This binding triggers the transition of S1B domains to the open state through allosteric interdomain crosstalk. Our findings provide detailed insight into coronavirus attachment, with possibilities of dual receptor usage and priming of entry as a means of immune escape.

Date: 2023
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-023-06599-z Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:624:y:2023:i:7990:d:10.1038_s41586-023-06599-z

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-023-06599-z

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().