SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity
File(s)
Author(s)
Type
Journal Article
Abstract
The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARS-CoV-2 spike binds biliverdin and bilirubin, the tetrapyrrole products of heme metabolism, with nanomolar affinity. Using cryo–electron microscopy and x-ray crystallography, we mapped the tetrapyrrole interaction pocket to a deep cleft on the spike N-terminal domain (NTD). At physiological concentrations, biliverdin significantly dampened the reactivity of SARS-CoV-2 spike with immune sera and inhibited a subset of neutralizing antibodies. Access to the tetrapyrrole-sensitive epitope is gated by a flexible loop on the distal face of the NTD. Accompanied by profound conformational changes in the NTD, antibody binding requires relocation of the gating loop, which folds into the cleft vacated by the metabolite. Our results indicate that SARS-CoV-2 spike NTD harbors a dominant epitope, access to which can be controlled by an allosteric mechanism that is regulated through recruitment of a metabolite.
Date Issued
2021-05-01
Date Acceptance
2021-04-02
Citation
Science Advances, 2021, 7 (22), pp.1-14
ISSN
2375-2548
Publisher
American Association for the Advancement of Science
Start Page
1
End Page
14
Journal / Book Title
Science Advances
Volume
7
Issue
22
Copyright Statement
© 2021
The Authors, some
rights reserved;
exclusive licensee
American Association
for the Advancement
of Science. No claim to
original U.S.Government
Works. Distributed
under a Creative
Commons Attribution
License 4.0 (CC BY).
The Authors, some
rights reserved;
exclusive licensee
American Association
for the Advancement
of Science. No claim to
original U.S.Government
Works. Distributed
under a Creative
Commons Attribution
License 4.0 (CC BY).
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000655906900036&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
CRYO-EM STRUCTURE
MONOCLONAL-ANTIBODIES
SPIKE
SYSTEM
VALIDATION
MOLPROBITY
EFFICIENT
BINDING
MODELS
PHENIX
Publication Status
Published
Article Number
ARTN eabg7607
Date Publish Online
2021-05-28