独特的蛋氨酸-芳环相互作用控制钙调蛋白氧化还原传感器。
Unique methionine-aromatic interactions govern the calmodulin redox sensor.
机构信息
University of Wisconsin-La Crosse, 1725 State Street, La Crosse, WI, USA.
University of Wisconsin-La Crosse, 1725 State Street, La Crosse, WI, USA.
出版信息
Biochem Biophys Res Commun. 2018 Oct 20;505(1):236-241. doi: 10.1016/j.bbrc.2018.09.052. Epub 2018 Sep 20.
Calmodulin contains multiple redox sensitive methionines whose oxidation alters the regulation of numerous targets. Molecular dynamics simulations were used to define the molecular principles that govern how calmodulin is structurally poised to detect and respond to methionine oxidation. We found that calmodulin's open and closed states were preferentially stabilized by unique, redox sensitive, methionine-aromatic interactions. Key methionine-aromatic interactions were coupled to reorientation of EF hand helices. Methionine to glutamine substitutions designed to mimic methionine oxidation strongly altered conformational transitions by modulating the strength of methionine-aromatic interactions. Together, these results suggest a broadly applicable redox sensing mechanism though which methionine oxidation by cellular oxidants alters the strength of methionine-aromatic interactions critical for functional protein dynamics.
钙调蛋白包含多个氧化还原敏感的蛋氨酸，其氧化会改变对众多靶标的调节。分子动力学模拟用于定义控制钙调蛋白如何在结构上准备好检测和响应蛋氨酸氧化的分子原理。我们发现，钙调蛋白的开放和关闭状态优先由独特的、氧化还原敏感的、蛋氨酸-芳香族相互作用稳定。关键的蛋氨酸-芳香族相互作用与 EF 手螺旋的重排偶联。设计用于模拟蛋氨酸氧化的蛋氨酸到谷氨酰胺取代强烈改变构象转变，通过调节蛋氨酸-芳香族相互作用的强度。总之，这些结果表明存在一种广泛适用的氧化还原感应机制，通过该机制，细胞氧化剂的蛋氨酸氧化会改变对功能蛋白动力学至关重要的蛋氨酸-芳香族相互作用的强度。
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