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Structural basis of receptor recognition by SARS-CoV-2

Author

Listed:
  • Jian Shang

    (University of Minnesota)

  • Gang Ye

    (University of Minnesota)

  • Ke Shi

    (University of Minnesota)

  • Yushun Wan

    (University of Minnesota)

  • Chuming Luo

    (University of Minnesota)

  • Hideki Aihara

    (University of Minnesota)

  • Qibin Geng

    (University of Minnesota)

  • Ashley Auerbach

    (University of Minnesota)

  • Fang Li

    (University of Minnesota)

Abstract

A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans, causing COVID-191,2. A key to tackling this pandemic is to understand the receptor recognition mechanism of the virus, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor—angiotensin-converting enzyme 2 (ACE2)—in humans3,4. Here we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 (engineered to facilitate crystallization) in complex with ACE2. In comparison with the SARS-CoV RBD, an ACE2-binding ridge in SARS-CoV-2 RBD has a more compact conformation; moreover, several residue changes in the SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD–ACE2 interface. These structural features of SARS-CoV-2 RBD increase its ACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus that is closely related to SARS-CoV-2, also uses human ACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in ACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies that target receptor recognition by SARS-CoV-2.

Suggested Citation

  • Jian Shang & Gang Ye & Ke Shi & Yushun Wan & Chuming Luo & Hideki Aihara & Qibin Geng & Ashley Auerbach & Fang Li, 2020. "Structural basis of receptor recognition by SARS-CoV-2," Nature, Nature, vol. 581(7807), pages 221-224, May.
    • Handle: RePEc:nat:nature:v:581:y:2020:i:7807:d:10.1038_s41586-020-2179-y
    DOI: 10.1038/s41586-020-2179-y
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    Cited by:

    1. Tomokazu Yamaguchi & Midori Hoshizaki & Takafumi Minato & Satoru Nirasawa & Masamitsu N. Asaka & Mayumi Niiyama & Masaki Imai & Akihiko Uda & Jasper Fuk-Woo Chan & Saori Takahashi & Jianbo An & Akari , 2021. "ACE2-like carboxypeptidase B38-CAP protects from SARS-CoV-2-induced lung injury," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
    2. Milad Haghani & Pegah Varamini, 2021. "Temporal evolution, most influential studies and sleeping beauties of the coronavirus literature," Scientometrics, Springer;Akadémiai Kiadó, vol. 126(8), pages 7005-7050, August.
    3. Anna R. Mäkelä & Hasan Uğurlu & Liina Hannula & Ravi Kant & Petja Salminen & Riku Fagerlund & Sanna Mäki & Anu Haveri & Tomas Strandin & Lauri Kareinen & Jussi Hepojoki & Suvi Kuivanen & Lev Levanov &, 2023. "Intranasal trimeric sherpabody inhibits SARS-CoV-2 including recent immunoevasive Omicron subvariants," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    4. Zepeng Xu & Xinrui Kang & Pu Han & Pei Du & Linjie Li & Anqi Zheng & Chuxia Deng & Jianxun Qi & Xin Zhao & Qihui Wang & Kefang Liu & George Fu Gao, 2022. "Binding and structural basis of equine ACE2 to RBDs from SARS-CoV, SARS-CoV-2 and related coronaviruses," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    5. Shouheng Jin & Xing He & Ling Ma & Zhen Zhuang & Yiliang Wang & Meng Lin & Sihui Cai & Lu Wei & Zheyu Wang & Zhiyao Zhao & Yaoxing Wu & Lin Sun & Chunwei Li & Weihong Xie & Yong Zhao & Zhou Songyang &, 2022. "Suppression of ACE2 SUMOylation protects against SARS-CoV-2 infection through TOLLIP-mediated selective autophagy," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    6. Byung Uk Lee, 2021. "Why Does the SARS-CoV-2 Delta VOC Spread So Rapidly? Universal Conditions for the Rapid Spread of Respiratory Viruses, Minimum Viral Loads for Viral Aerosol Generation, Effects of Vaccination on Viral," IJERPH, MDPI, vol. 18(18), pages 1-6, September.
    7. Hossein Hozhabri & Francesca Piceci Sparascio & Hamidreza Sohrabi & Leila Mousavifar & René Roy & Daniela Scribano & Alessandro De Luca & Cecilia Ambrosi & Meysam Sarshar, 2020. "The Global Emergency of Novel Coronavirus (SARS-CoV-2): An Update of the Current Status and Forecasting," IJERPH, MDPI, vol. 17(16), pages 1-35, August.
    8. Gang Ye & Bin Liu & Fang Li, 2022. "Cryo-EM structure of a SARS-CoV-2 omicron spike protein ectodomain," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    9. Yifan Wang & Caixuan Liu & Chao Zhang & Yanxing Wang & Qin Hong & Shiqi Xu & Zuyang Li & Yong Yang & Zhong Huang & Yao Cong, 2022. "Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    10. Xuanming Guo & Jianli Cao & Jian-Piao Cai & Jiayan Wu & Jiangang Huang & Pallavi Asthana & Sheung Kin Ken Wong & Zi-Wei Ye & Susma Gurung & Yijing Zhang & Sheng Wang & Zening Wang & Xin Ge & Hiu Yee K, 2022. "Control of SARS-CoV-2 infection by MT1-MMP-mediated shedding of ACE2," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    11. David Gomez-Zepeda & Danielle Arnold-Schild & Julian Beyrle & Arthur Declercq & Ralf Gabriels & Elena Kumm & Annica Preikschat & Mateusz Krzysztof Łącki & Aurélie Hirschler & Jeewan Babu Rijal & Chris, 2024. "Thunder-DDA-PASEF enables high-coverage immunopeptidomics and is boosted by MS2Rescore with MS2PIP timsTOF fragmentation prediction model," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    12. Fabian Zech & Daniel Schniertshauer & Christoph Jung & Alexandra Herrmann & Arne Cordsmeier & Qinya Xie & Rayhane Nchioua & Caterina Prelli Bozzo & Meta Volcic & Lennart Koepke & Janis A. Müller & Jan, 2021. "Spike residue 403 affects binding of coronavirus spikes to human ACE2," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    13. Maximilian A. Funk & Judith Leitner & Marlene C. Gerner & Jasmin M. Hammerler & Benjamin Salzer & Manfred Lehner & Claire Battin & Simon Gumpelmair & Karin Stiasny & Katharina Grabmeier-Pfistershammer, 2023. "Interrogating ligand-receptor interactions using highly sensitive cellular biosensors," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    14. Cedric C. S. Tan & Su Datt Lam & Damien Richard & Christopher J. Owen & Dorothea Berchtold & Christine Orengo & Meera Surendran Nair & Suresh V. Kuchipudi & Vivek Kapur & Lucy van Dorp & François Ball, 2022. "Transmission of SARS-CoV-2 from humans to animals and potential host adaptation," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    15. David Chmielewski & Eric A. Wilson & Grigore Pintilie & Peng Zhao & Muyuan Chen & Michael F. Schmid & Graham Simmons & Lance Wells & Jing Jin & Abhishek Singharoy & Wah Chiu, 2023. "Structural insights into the modulation of coronavirus spike tilting and infectivity by hinge glycans," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    16. Mohamed A. Farrag & Haitham M. Amer & Rauf Bhat & Maaweya E. Hamed & Ibrahim M. Aziz & Ayman Mubarak & Turki M Dawoud & Sami G Almalki & Fayez Alghofaili & Ahmad K. Alnemare & Raid Saleem Al-Baradi & , 2021. "SARS-CoV-2: An Overview of Virus Genetics, Transmission, and Immunopathogenesis," IJERPH, MDPI, vol. 18(12), pages 1-14, June.
    17. Dhiraj Mannar & James W. Saville & Chad Poloni & Xing Zhu & Alison Bezeruk & Keith Tidey & Sana Ahmed & Katharine S. Tuttle & Faezeh Vahdatihassani & Spencer Cholak & Laura Cook & Theodore S. Steiner , 2024. "Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    18. Peter Radvak & Hyung-Joon Kwon & Martina Kosikova & Uriel Ortega-Rodriguez & Ruoxuan Xiang & Je-Nie Phue & Rong-Fong Shen & James Rozzelle & Neeraj Kapoor & Taylor Rabara & Jeff Fairman & Hang Xie, 2021. "SARS-CoV-2 B.1.1.7 (alpha) and B.1.351 (beta) variants induce pathogenic patterns in K18-hACE2 transgenic mice distinct from early strains," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    19. Oskar Staufer & Kapil Gupta & Jochen Estebano Hernandez Bücher & Fabian Kohler & Christian Sigl & Gunjita Singh & Kate Vasileiou & Ana Yagüe Relimpio & Meline Macher & Sebastian Fabritz & Hendrik Diet, 2022. "Synthetic virions reveal fatty acid-coupled adaptive immunogenicity of SARS-CoV-2 spike glycoprotein," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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