Literature detail

Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.

Jun Lan¹ Jiwan Ge¹ Jinfang Yu¹ Sisi Shan² Huan Zhou³ Shilong Fan¹ Qi Zhang² Xuanling Shi² Qisheng Wang³ Linqi Zhang⁴ Xinquan Wang⁵

Affiliations 5 institutions

The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China.
Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China.
Shanghai Synchrotron Radiation Facility, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai, China.
Center for Global Health and Infectious Diseases, Comprehensive AIDS Research Center, Beijing Advanced Innovation Center for Structural Biology, School of Medicine, Tsinghua University, Beijing, China. [email protected].
The Ministry of Education Key Laboratory of Protein Science, Beijing Advanced Innovation Center for Structural Biology, Beijing Frontier Research Center for Biological Structure, Collaborative Innovation Center for Biotherapy, School of Life Sciences, Tsinghua University, Beijing, China. [email protected].

PMID 32225176 2020 Nature eng ppublish

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Article

Publication summary

A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.

Amino Acid Sequence Angiotensin-Converting Enzyme 2 Antibodies, Neutralizing Betacoronavirus Binding Sites Conserved Sequence Crystallography, X-Ray Epitopes Evolution, Molecular Humans Hydrogen Bonding Models, Molecular Peptidyl-Dipeptidase A Protein Binding Protein Domains Receptors, Virus Salts SARS-CoV-2

Structured evidence records

Evidence records

3 total

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.70

Key finding

Structural and sequence analyses of the spike receptor-binding domain showed that SARS-CoV-2 and SARS-CoV exhibit convergent evolution for improved ACE2 binding.

Virus

Host

Location

Supporting text

Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs.

Genes or proteins: spike; receptor-binding domain
Analysis methods: structural analysis; sequence alignment

Molecular Adaptation 1 records

Molecular Adaptation Extraction confidence 0.90

Key finding

SARS-CoV-2 spike receptor-binding domain shows molecular adaptation via conserved and convergently evolved residues that enhance ACE2 receptor binding compared to related coronaviruses.

Virus

Host

Location

Supporting text

We determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, and similarity in structure and sequence indicates convergent evolution between SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2.

Genes or proteins: spike; RBD
Receptors: ACE2
Mechanism types: receptor_binding; host_factor_interaction; convergent_evolution

Receptor Usage 1 records

Receptor Usage Extraction confidence 1.00

Key finding

SARS-CoV-2 spike protein binds the ACE2 receptor in a mode nearly identical to that of SARS-CoV, indicating shared receptor usage and conserved binding residues.

Virus

Host

Location

Supporting text

We determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor.

Method: crystal structure determination; structural analysis
Receptors: ACE2

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References

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Evidence overview

Evidence 3

Types 3

Virus 1

Host 1

Evidence types

Genomic Evolution 1 Molecular Adaptation 1 Receptor Usage 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: Nature
Volume / Issue / Pages: 581 / 7807 / 215-220
ISSN: 1476-4687
Journal country: England
DOI: 10.1038/s41586-020-2180-5