Imperial College London
Alternate

ProfessorGeorgiosKassiotis

Faculty of Medicine, Department of Infectious Disease

Professor of Retrovirology
 
 
 
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Contact

 

g.kassiotis Website

 
 
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Location

 

Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Rosa:2021:10.1126/sciadv.abg7607,
author = {Rosa, A and Pye, VE and Graham, C and Muir, L and Seow, J and Ng, KW and Cook, NJ and Rees-Spear, C and Parker, E and dos, Santos MS and Rosadas, C and Susana, A and Rhys, H and Nans, A and Masino, L and Roustan, C and Christodoulou, E and Ulferts, R and Wrobel, AG and Short, C-E and Fertleman, M and Sanders, RW and Heaney, J and Spyer, M and Kjaer, S and Riddell, A and Malim, MH and Beale, R and MacRae, J and Taylor, GP and Nastouli, E and van, Gils MJ and Rosenthal, PB and Pizzato, M and McClure, MO and Tedder, RS and Kassiotis, G and McCoy, LE and Doores, KJ and Cherepanov, P},
doi = {10.1126/sciadv.abg7607},
journal = {Science Advances},
pages = {1--14},
title = {SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity},
url = {http://dx.doi.org/10.1126/sciadv.abg7607},
volume = {7},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Rosa,A
AU  - Pye,VE
AU  - Graham,C
AU  - Muir,L
AU  - Seow,J
AU  - Ng,KW
AU  - Cook,NJ
AU  - Rees-Spear,C
AU  - Parker,E
AU  - dos,Santos MS
AU  - Rosadas,C
AU  - Susana,A
AU  - Rhys,H
AU  - Nans,A
AU  - Masino,L
AU  - Roustan,C
AU  - Christodoulou,E
AU  - Ulferts,R
AU  - Wrobel,AG
AU  - Short,C-E
AU  - Fertleman,M
AU  - Sanders,RW
AU  - Heaney,J
AU  - Spyer,M
AU  - Kjaer,S
AU  - Riddell,A
AU  - Malim,MH
AU  - Beale,R
AU  - MacRae,J
AU  - Taylor,GP
AU  - Nastouli,E
AU  - van,Gils MJ
AU  - Rosenthal,PB
AU  - Pizzato,M
AU  - McClure,MO
AU  - Tedder,RS
AU  - Kassiotis,G
AU  - McCoy,LE
AU  - Doores,KJ
AU  - Cherepanov,P
DO  - 10.1126/sciadv.abg7607
EP  - 14
PY  - 2021///
SN  - 2375-2548
SP  - 1
TI  - SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity
T2  - Science Advances
UR  - http://dx.doi.org/10.1126/sciadv.abg7607
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000655906900036&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://www.science.org/doi/10.1126/sciadv.abg7607
UR  - http://hdl.handle.net/10044/1/95486
VL  - 7
ER  -
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