Protein nanopore reveals the renin-angiotensin system crosstalk with single-amino-acid resolution.
Nat Chem
; 15(4): 578-586, 2023 04.
Article
in English
| MEDLINE | ID: covidwho-2264706
ABSTRACT
The discovery of crosstalk effects on the renin-angiotensin system (RAS) is limited by the lack of approaches to quantitatively monitor, in real time, multiple components with subtle differences and short half-lives. Here we report a nanopore framework to quantitatively determine the effect of the hidden crosstalk between angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) on RAS. By developing an engineered aerolysin nanopore capable of single-amino-acid resolution, we show that the ACE can be selectively inhibited by ACE2 to prevent cleavage of angiotensin I, even when the concentration of ACE is more than 30-fold higher than that of ACE2. We also show that the activity of ACE2 for cleaving angiotensin peptides is clearly suppressed by the spike protein of SARS-CoV-2. This leads to the relaxation of ACE and the increased probability of accumulation of the principal effector angiotensin II. The spike protein of the SARS-CoV-2 Delta variant is demonstrated to have a much greater impact on the crosstalk than the wild type.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Nanopores
/
COVID-19
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Nat Chem
Journal subject:
Chemistry
Year:
2023
Document Type:
Article
Affiliation country:
S41557-023-01139-8
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