tetano
Editor, Senior Moderator
J Biol Chem
. 2020 Oct 29;jbc.RA120.015303.
doi: 10.1074/jbc.RA120.015303. Online ahead of print.
High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity
Jinghua Lu[SUP] 1 [/SUP], Peter D Sun[SUP] 1 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2 spike protein; angiotensin converting enzyme 2; carboxypeptidase; enzymatic activity; fluorescence resonance energy transfer (FRET); pathogenesis; renin angiotensin system; viral protein.
. 2020 Oct 29;jbc.RA120.015303.
doi: 10.1074/jbc.RA120.015303. Online ahead of print.
High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity
Jinghua Lu[SUP] 1 [/SUP], Peter D Sun[SUP] 1 [/SUP]
Affiliations
- PMID: 33122196
- DOI: 10.1074/jbc.RA120.015303
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.
Keywords: SARS-CoV-2 spike protein; angiotensin converting enzyme 2; carboxypeptidase; enzymatic activity; fluorescence resonance energy transfer (FRET); pathogenesis; renin angiotensin system; viral protein.