Structural basis of receptor recognition by SARS-CoV-2
Open Access
- 30 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 581 (7807), 221-224
- https://doi.org/10.1038/s41586-020-2179-y
Abstract
A novel SARS-like coronavirus (SARS-CoV-2) recently emerged and is rapidly spreading in humans1,2. A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor - human ACE2 (hACE2)3,4. Here we determined the crystal structure of the SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex with hACE2. Compared with the SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV and RaTG13 in hACE2 recognition shed light on potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies targeting receptor recognition by SARS-CoV-2.Keywords
This publication has 38 references indexed in Scilit:
- Mechanisms of Host Receptor Adaptation by Severe Acute Respiratory Syndrome CoronavirusOnline Journal of Public Health Informatics, 2012
- Overview of theCCP4 suite and current developmentsActa crystallographica. Section D, Structural biology, 2011
- Coronaviruses post-SARS: update on replication and pathogenesisNature Reviews Microbiology, 2009
- The spike protein of SARS-CoV — a target for vaccine and therapeutic developmentNature Reviews Microbiology, 2009
- Structural Analysis of Major Species Barriers between Humans and Palm Civets for Severe Acute Respiratory Syndrome Coronavirus InfectionsJournal of Virology, 2008
- HDAC inhibitor reduces cytokine storm and facilitates induction of chimerism that reverses lupus in anti-CD3 conditioning regimenProceedings of the National Academy of Sciences of the United States of America, 2008
- Structure of SARS Coronavirus Spike Receptor-Binding Domain Complexed with ReceptorScience, 2005
- Coot: model-building tools for molecular graphicsActa crystallographica. Section D, Structural biology, 2004
- Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirusNature, 2003
- [20] Processing of X-ray diffraction data collected in oscillation modeMethods in Enzymology, 1997