南京大学龙亿涛团队报道了蛋白质纳米孔以单氨基酸分辨率揭示肾素-血管紧张素系统串扰。相关研究成果发表在2023年2月20日出版的《自然—化学》。

肾素-血管紧张素系统(RAS)的串扰效应的发现，由于缺乏实时定量监测具有细微差异和短半衰期的多种成分的方法而受到限制。

该文中，研究人员报道了一种纳米孔框架，以定量确定血管紧张素转换酶（ACE）和血管紧张素转化酶2（ACE2）之间的隐性串扰对RAS的影响。通过开发一种能够分解单个氨基酸的工程化溶气素纳米孔，研究人员发现ACE可以被ACE2选择性地抑制，以防止血管紧张素I的裂解，即使ACE的浓度比ACE2的浓度高30倍以上。研究还表明，SARS-CoV-2的刺突蛋白明显抑制ACE2切割血管紧张素肽的活性。这导致ACE的松弛和主要效应血管紧张素II积聚的可能性增加。SARS-CoV-2 Delta变体的刺突蛋白被证明对串扰的影响比野生型大得多。

附：英文原文

Title: Protein nanopore reveals the renin–angiotensin system crosstalk with single-amino-acid resolution

Author: Jiang, Jie, Li, Meng-Yin, Wu, Xue-Yuan, Ying, Yi-Lun, Han, Huan-Xing, Long, Yi-Tao

Issue&Volume: 2023-02-20

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.

DOI: 10.1038/s41557-023-01139-8

Source: https://www.nature.com/articles/s41557-023-01139-8