High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity.
High affinity binding of SARS-CoV-2 spike protein enhances ACE2 carboxypeptidase activity.
复制标题
DOI：
10.1074/jbc.ra120.015303
复制
发表时间：
2020-12-25
期刊：
影响因子：
--
通讯作者：
Sun PD
中科院分区：
文献类型：
--
作者：
Lu J;Sun PD
新型严重急性呼吸综合征冠状病毒（SARS-CoV-2）已出现大流行并引发全球公共卫生危机。人血管紧张素转换酶 2（ACE2）被确定为 SARS-CoV-2 的进入受体。作为一种羧肽酶，ACE2 可以裂解除血管紧张素 II 之外的许多生物底物，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将如何影响 ACE2 的酶活性。令人惊讶的是，SARS-CoV-2 三聚刺突蛋白相对于模型肽底物（例如 caspase-1 底物和缓激肽类似物），将 ACE2 蛋白水解活性提高了约 3-10 倍。 ACE2 酶功能的增强是通过 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 活性的潜力，这可能与 COVID-19 相关的心血管症状有关。
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.