SARS-CoV-2 can recruit a heme metabolite to evade antibody immunity

被引:86
作者
Rosa, Annachiara [1 ]
Pye, Valerie E. [1 ]
Graham, Carl [2 ]
Muir, Luke [3 ]
Seow, Jeffrey [2 ]
Ng, Kevin W. [4 ]
Cook, Nicola J. [1 ]
Rees-Spear, Chloe [3 ]
Parker, Eleanor [5 ]
dos Santos, Mariana Silva [6 ]
Rosadas, Carolina [5 ]
Susana, Alberto [7 ]
Rhys, Hefin [8 ]
Nans, Andrea [9 ]
Masino, Laura [9 ]
Roustan, Chloe [9 ]
Christodoulou, Evangelos [9 ]
Ulferts, Rachel [10 ]
Wrobel, Antoni G. [11 ]
Short, Charlotte-Eve [5 ]
Fertleman, Michael [12 ]
Sanders, Rogier W. [13 ,14 ]
Heaney, Judith [15 ,16 ]
Spyer, Moira [15 ,16 ,17 ]
Kjaer, Svend [9 ]
Riddell, Andy [8 ]
Malim, Michael H. [2 ]
Beale, Rupert [10 ]
MacRae, James, I [6 ]
Taylor, Graham P. [5 ]
Nastouli, Eleni [15 ,16 ,17 ]
van Gils, Marit J. [13 ]
Rosenthal, Peter B. [18 ]
Pizzato, Massimo [7 ]
McClure, Myra O. [5 ]
Tedder, Richard S. [5 ]
Kassiotis, George [4 ,5 ]
McCoy, Laura E. [3 ]
Doores, Katie J. [2 ]
Cherepanov, Peter [1 ,5 ]
机构
[1] Francis Crick Inst, Chromatin Struct & Mobile DNA Lab, London, England
[2] Kings Coll London, Sch Immunol & Microbial Sci, Dept Infect Dis, London, England
[3] UCL, Inst Immun & Transplantat, Div Infect & Immun, London, England
[4] Francis Crick Inst, Retroviral Immunol Lab, London, England
[5] Imperial Coll London, Dept Infect Dis, St Marys Campus, London, England
[6] Francis Crick Inst, Metabol Sci Technol Platform, London, England
[7] Univ Trento, Dept Cellular Computat & Integrat Biol, Trento, Italy
[8] Francis Crick Inst, Flow Cytometry Sci & Technol Platform, London, England
[9] Francis Crick Inst, Struct Biol Sci Technol Platform, London, England
[10] Francis Crick Inst, Cell Biol Infect Lab, London, England
[11] Francis Crick Inst, Struct Biol Dis Proc Lab, London, England
[12] Imperial Coll London, Cutrale Perioperat & Ageing Grp, London, England
[13] Univ Amsterdam, Amsterdam Inst Infect & Immun, Dept Med Microbiol, Amsterdam UMC, Amsterdam, Netherlands
[14] Cornell Univ, Weill Med Coll, New York, NY 10021 USA
[15] Univ Coll London Hosp NHS Fdn Trust, Adv Pathogen Diagnost Unit, London, England
[16] Francis Crick Inst, Crick COVID 19 Consortium, London, England
[17] UCL Great Ormond St Inst Child Hlth, Dept Infect Immun & Inflammat, London, England
[18] Francis Crick Inst, Struct Biol Cells & Viruses Lab, London, England
基金
英国惠康基金; 美国国家卫生研究院; 英国医学研究理事会;
关键词
CRYO-EM STRUCTURE; MONOCLONAL-ANTIBODIES; SPIKE; SYSTEM; VALIDATION; MOLPROBITY; EFFICIENT; BINDING; MODELS; PHENIX;
D O I
10.1126/sciadv.abg7607
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The coronaviral spike is the dominant viral antigen and the target of neutralizing antibodies. We show that SARSCoV-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.
引用
收藏
页数:14
相关论文
共 73 条
  • [41] Punjani A, 2017, NAT METHODS, V14, P290, DOI [10.1038/nmeth.4169, 10.1038/NMETH.4169]
  • [42] Rambaut A, 2021, PRELIMINARY GENOMIC
  • [43] Deciphering key features in protein structures with the new ENDscript server
    Robert, Xavier
    Gouet, Patrice
    [J]. NUCLEIC ACIDS RESEARCH, 2014, 42 (W1) : W320 - W324
  • [44] Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model
    Rogers, Thomas F.
    Zhao, Fangzhu
    Huang, Deli
    Beutler, Nathan
    Burns, Alison
    He, Wan-Ting
    Limbo, Oliver
    Smith, Chloe
    Song, Ge
    Woehl, Jordan
    Yang, Linlin
    Abbott, Robert K.
    Callaghan, Sean
    Garcia, Elijah
    Hurtado, Jonathan
    Parren, Mara
    Peng, Linghang
    Ramirez, Sydney
    Ricketts, James
    Ricciardi, Michael J.
    Rawlings, Stephen A.
    Wu, Nicholas C.
    Yuan, Meng
    Smith, Davey M.
    Nemazee, David
    Teijaro, John R.
    Voss, James E.
    Wilson, Ian A.
    Andrabi, Raiees
    Briney, Bryan
    Landais, Elise
    Sok, Devin
    Jardine, Joseph G.
    Burton, Dennis R.
    [J]. SCIENCE, 2020, 369 (6506) : 956 - +
  • [45] Optimal determination of particle orientation, absolute hand, and contrast loss in single-particle electron cryomicroscopy
    Rosenthal, PB
    Henderson, R
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2003, 333 (04) : 721 - 745
  • [46] Amyloid structure determination in RELION-3.1
    Scheres, Sjors H. W.
    [J]. ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2020, 76 : 94 - 101
  • [47] Prevention of overfitting in cryo-EM structure determination
    Scheres, Sjors H. W.
    Chen, Shaoxia
    [J]. NATURE METHODS, 2012, 9 (09) : 853 - 854
  • [48] Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses
    Schmidt, Fabian
    Weisblum, Yiska
    Muecksch, Frauke
    Hoffmann, Hans-Heinrich
    Michailidis, Eleftherios
    Lorenzi, Julio C. C.
    Mendoza, Pilar
    Rutkowska, Magdalena
    Bednarski, Eva
    Gaebler, Christian
    Agudelo, Marianna
    Cho, Alice
    Wang, Zijun
    Gazumyan, Anna
    Cipolla, Melissa
    Caskey, Marina
    Robbiani, Davide F.
    Nussenzweig, Michel C.
    Rice, Charles M.
    Hatziioannou, Theodora
    Bieniasz, Paul D.
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2020, 217 (11)
  • [49] MYELOPEROXIDASE OF LEUCOCYTE OF NORMAL HUMAN BLOOD .1. CONTENT AND LOCALIZATION
    SCHULTZ, J
    KAMINKER, K
    [J]. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1962, 96 (03) : 465 - &
  • [50] Longitudinal observation and decline of neutralizing antibody responses in the three months following SARS-CoV-2 infection in humans
    Seow, Jeffrey
    Graham, Carl
    Merrick, Blair
    Acors, Sam
    Pickering, Suzanne
    Steel, Kathryn J. A.
    Hemmings, Oliver
    O'Byrne, Aoife
    Kouphou, Neophytos
    Galao, Rui Pedro
    Betancor, Gilberto
    Wilson, Harry D.
    Signell, Adrian W.
    Winstone, Helena
    Kerridge, Claire
    Huettner, Isabella
    Jimenez-Guardeno, Jose M.
    Lista, Maria Jose
    Temperton, Nigel
    Snell, Luke B.
    Bisnauthsing, Karen
    Moore, Amelia
    Green, Adrian
    Martinez, Lauren
    Stokes, Brielle
    Honey, Johanna
    Izquierdo-Barras, Alba
    Arbane, Gill
    Patel, Amita
    Tan, Mark Kia Ik
    O'Connell, Lorcan
    O'Hara, Geraldine
    MacMahon, Eithne
    Douthwaite, Sam
    Nebbia, Gaia
    Batra, Rahul
    Martinez-Nunez, Rocio
    Shankar-Hari, Manu
    Edgeworth, Jonathan D.
    Neil, Stuart J. D.
    Malim, Michael H.
    Doores, Katie J.
    [J]. NATURE MICROBIOLOGY, 2020, 5 (12) : 1598 - +