Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2

Pengcheng Han; Linjie Li; Sheng Liu; Qisheng Wang; Di Zhang; Zepeng Xu; Pu Han; Xiaomei Li; Qi Peng; Chao Su; Baihan Huang; Dedong Li; Rong Zhang; Mingxiong Tian; Lutang Fu; Yuanzhu Gao; Xin Zhao; Kefang Liu; Jianxun Qi; George F Gao; Peiyi Wang

doi:10.1016/j.cell.2022.01.001

Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2

Cell. 2022 Feb 17;185(4):630-640.e10. doi: 10.1016/j.cell.2022.01.001. Epub 2022 Jan 6.

Authors

Pengcheng Han¹, Linjie Li², Sheng Liu³, Qisheng Wang⁴, Di Zhang⁵, Zepeng Xu⁵, Pu Han⁶, Xiaomei Li⁷, Qi Peng⁶, Chao Su⁸, Baihan Huang⁶, Dedong Li⁶, Rong Zhang⁶, Mingxiong Tian⁹, Lutang Fu³, Yuanzhu Gao³, Xin Zhao⁶, Kefang Liu⁶, Jianxun Qi¹⁰, George F Gao¹¹, Peiyi Wang¹²

Affiliations

¹ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; School of Medicine, Zhongda Hospital, Southeast University, NanJing 210009, China.
² CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.
³ Cryo-EM Center, Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China.
⁴ Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201204, China.
⁵ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; Faculty of Health Sciences, University of Macau, Macau 999078, China.
⁶ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
⁷ Cryo-EM Center, Shanxi Academy of Advanced Research and Innovation, Taiyuan 030032, China.
⁸ Department of Biomedical Sciences, City University of Hong Kong, Hong Kong 999077, China.
⁹ College of life Science, Shanxi University, Taiyuan 03006, China.
¹⁰ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
¹¹ CAS Key Laboratory of Pathogen Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: [email protected].
¹² Cryo-EM Center, Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: [email protected].

Abstract

The coronavirus disease 2019 (COVID-19) pandemic continues worldwide with many variants arising, some of which are variants of concern (VOCs). A recent VOC, omicron (B.1.1.529), which obtains a large number of mutations in the receptor-binding domain (RBD) of the spike protein, has risen to intense scientific and public attention. Here, we studied the binding properties between the human receptor ACE2 (hACE2) and the VOC RBDs and resolved the crystal and cryoelectron microscopy structures of the omicron RBD-hACE2 complex as well as the crystal structure of the delta RBD-hACE2 complex. We found that, unlike alpha, beta, and gamma, omicron RBD binds to hACE2 at a similar affinity to that of the prototype RBD, which might be due to compensation of multiple mutations for both immune escape and transmissibility. The complex structures of omicron RBD-hACE2 and delta RBD-hACE2 reveal the structural basis of how RBD-specific mutations bind to hACE2.

Keywords: RBD; VOCs; delta; hACE2; omicron; receptor-binding domain; structure; variants of concern.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Angiotensin-Converting Enzyme 2 / chemistry*
Cryoelectron Microscopy
Humans
Models, Molecular
Mutation / genetics
Phylogeny
Protein Binding
Protein Domains
Receptors, Virus / chemistry*
SARS-CoV-2 / chemistry*
Spike Glycoprotein, Coronavirus / chemistry
Spike Glycoprotein, Coronavirus / genetics
Spike Glycoprotein, Coronavirus / ultrastructure
Static Electricity
Structural Homology, Protein

Substances

Receptors, Virus
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Angiotensin-Converting Enzyme 2

Supplementary concepts

SARS-CoV-2 variants