Inter-domain communication in SARS-CoV-2 spike proteins controls protease-triggered cell entry

Qing E, Li P, Cooper L, Schulz S, Jäck HM, Rong L, Perlman S, Gallagher T (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Cell Reports Elsevier (Cell Press)

Book Volume: 39

Article Number: 110786

Journal Issue: 5

DOI: 10.1016/j.celrep.2022.110786

Abstract

SARS-CoV-2 continues to evolve into variants of concern (VOC), with greatest variability in the multidomain, entry-facilitating spike proteins. To recognize the significance of adaptive spike protein changes, we compare variant SARS-CoV-2 virus particles in several assays reflecting authentic virus-cell entry. Virus particles with adaptive changes in spike amino-terminal domains (NTDs) are hypersensitive to proteolytic activation of membrane fusion, an essential step in virus-cell entry. Proteolysis is within fusion domains (FDs), at sites over 10 nm from the VOC-specific NTD changes, indicating allosteric inter-domain control of fusion activation. In addition, NTD-specific antibodies block FD cleavage, membrane fusion, and virus-cell entry, suggesting restriction of inter-domain communication as a neutralization mechanism. Finally, using structure-guided mutagenesis, we identify an inter-monomer β sheet structure that facilitates NTD-to-FD transmissions and subsequent fusion activation. This NTD-to-FD axis that sensitizes viruses to infection and to NTD-specific antibody neutralization provides new context for understanding selective forces driving SARS-CoV-2 evolution.

Authors with CRIS profile

Sebastian Schulz Professur für Immunologie Hans-Martin Jäck Department of Molecular Immunology

Involved external institutions

Loyola University Chicago US United States (USA) (US) University of Iowa US United States (USA) (US) University of Illinois at Chicago US United States (USA) (US)

How to cite

APA:

Qing, E., Li, P., Cooper, L., Schulz, S., Jäck, H.-M., Rong, L.,... Gallagher, T. (2022). Inter-domain communication in SARS-CoV-2 spike proteins controls protease-triggered cell entry. Cell Reports, 39(5). https://doi.org/10.1016/j.celrep.2022.110786

MLA:

Qing, Enya, et al. "Inter-domain communication in SARS-CoV-2 spike proteins controls protease-triggered cell entry." Cell Reports 39.5 (2022).

BibTeX: Download