Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
Structural Immunology Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, Rockville, Maryland, USA.
J Biol Chem. 2020 Dec 25;295(52):18579-18588. doi: 10.1074/jbc.RA120.015303. Epub 2020 Oct 29.
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.
新型严重急性呼吸综合征冠状病毒（SARS-CoV-2）已引发全球公共卫生危机。人类血管紧张素转换酶 2（ACE2）被鉴定为 SARS-CoV-2 的进入受体。作为一种羧肽酶，ACE2 除了血管紧张素 II 外，还可切割许多生物底物，以控制血管舒张和血管通透性。鉴于 ACE2 和 SARS-CoV-2 刺突蛋白之间具有纳摩尔级的高亲和力，我们研究了这种相互作用如何影响 ACE2 的酶活性。令人惊讶的是，SARS-CoV-2 三聚体刺突蛋白使 ACE2 对模型肽底物（如半胱天冬酶-1 底物和缓激肽类似物）的蛋白水解活性增加了 3-10 倍。ACE2 酶功能的增强是由 SARS-CoV-2 刺突 RBD 结构域的结合介导的。这些结果强调了 SARS-CoV-2 感染增强 ACE2 活性的可能性，这可能与 COVID-19 相关的心血管症状有关。
