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

被引：78

作者：

Lu, Jinghua ^{[1
]}

Sun, Peter D. ^{[1
]}

机构：

[1] NIAID, Struct Immunol Sect, Lab Immunogenet, Rockville, MD 20852 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2020年 / 295卷 / 52期

基金：

美国国家卫生研究院;

关键词：

viral protein; carboxypeptidase; renin angiotensin system; fluorescence resonance energy transfer (FRET); pathogenesis; angiotensin converting enzyme 2; enzymatic activity; SARS-CoV-2 spike protein; ANGIOTENSIN-CONVERTING ENZYME-2; DYNORPHIN; RECEPTOR;

D O I：

10.1074/jbc.RA120.015303

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 similar to 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.

引用

页码：18579 / 18588

页数：10

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