Biomechanical characterization of SARS-CoV-2 spike RBD and human ACE2 protein-protein interaction.

Biophysical Journal
Wenpeng CaoX. Frank Zhang

Abstract

The current COVID-19 pandemic has led to a devastating impact across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (the virus causing COVID-19) is known to use the receptor-binding domain (RBD) at viral surface spike (S) protein to interact with the angiotensin-converting enzyme 2 (ACE2) receptor expressed on many human cell types. The RBD-ACE2 interaction is a crucial step to mediate the host cell entry of SARS-CoV-2. Recent studies indicate that the ACE2 interaction with the SARS-CoV-2 S protein has a higher affinity than its binding with the structurally identical S protein of SARS-CoV-1, the virus causing the 2002-2004 SARS outbreak. However, the biophysical mechanism behind such binding affinity difference is unclear. This study utilizes combined single-molecule force spectroscopy and steered molecular dynamics (SMD) simulation approaches to quantify the specific interactions between SARS-CoV-2 or SARS-CoV-1 RBD and ACE2. Depending on the loading rates, the unbinding forces between SARS-CoV-2 RBD and ACE2 range from 70 to 105 pN and are 30-40% higher than those of SARS-CoV-1 RBD and ACE2 under similar loading rates. SMD results indicate that SARS-CoV-2 RBD interacts with the N-linked glycan on Asn...Continue Reading

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Citations

Mar 11, 2021·Biophysical Journal·Tamar SchlickM Madan Babu
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Datasets Mentioned

BETA
AY278488.2
QHD43416.1
AF291820.1
AFS88936.1

Methods Mentioned

BETA
atomic force microscopy
AFM
PCR
transfection
electrophoresis
force
glycosylation
pull-off

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