High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity.

The Journal of Biological Chemistry
Jinghua Lu, Peter D Sun

Abstract

The novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) has emerged to a pandemic and caused global public health crisis. Human angiotensin-converting enzyme 2(ACE2) was identified as the entry receptor for SARS-CoV-2. As a carboxypeptidase, ACE2 cleaves many biological substrates besides angiotensin II to control vasodilatation and vascular permeability. Given the nanomolar high affinity between ACE2 and SARS-CoV-2 spike protein, we investigated how this interaction would affect the enzymatic activity of ACE2. Surprisingly, SARS-CoV-2 trimeric spike protein increased ACE2 proteolytic activity ∼3-10 fold against model peptide substrates, such as caspase-1 substrate and Bradykinin-analog. The enhancement in ACE2 enzymatic function was mediated by the binding of SARS-CoV-2 spike RBD domain. These results highlighted the potential for SARS-CoV-2 infection to enhance ACE2 activity, which may be relevant to the cardiovascular symptoms associated with COVID-19.

References

Jan 1, 1989·Advances in Experimental Medicine and Biology·I A Sheikh, A P Kaplan
Oct 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·C Chavkin, A Goldstein
Aug 30, 2000·Pain·R M Caudle, A J Mannes
Jan 30, 2002·The Journal of Biological Chemistry·Chad VickersPeter Tummino
Feb 3, 2004·The Journal of Biological Chemistry·Paul TowlerMichael W Pantoliano
Apr 28, 2004·Trends in Endocrinology and Metabolism : TEM·Louise M BurrellMark E Cooper
Jul 8, 2005·Nature·Yumiko ImaiJosef M Penninger
Sep 5, 2008·American Journal of Physiology. Cell Physiology·Patricia E GallagherE Ann Tallant
Feb 11, 2014·Current Hypertension Reports·Jasmina VaragicCarlos M Ferrario
Jan 25, 2020·The New England Journal of Medicine·Na ZhuUNKNOWN China Novel Coronavirus Investigating and Research Team
Feb 23, 2020·Science·Daniel WrappJason S McLellan
Feb 23, 2020·The Lancet. Respiratory Medicine·Zhe XuFu-Sheng Wang
Apr 1, 2020·Nature·Jian ShangFang Li
May 7, 2020·Annals of Internal Medicine·Dominic WichmannStefan Kluge
Jun 9, 2020·MedRxiv : the Preprint Server for Health Sciences·Bruna Gg PintoHelder I Nakaya

❮ Previous
Next ❯

Citations

Mar 4, 2021·The Journal of Physical Chemistry. B·Billy J Williams-NoonanIrene Yarovsky

❮ Previous
Next ❯

Datasets Mentioned

BETA
MN908947

Methods Mentioned

BETA
transgenic
FRET
size exclusion chromatography
chips

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.