Eichmann Cédric, Tzitzilonis Christos, Nakamura Tomohiro, Kwiatkowski Witek, Maslennikov Innokentiy, Choe Senyon, Lipton Stuart A, Riek Roland
Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, CH-8093 Zürich, Switzerland.
Structural Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
J Mol Biol. 2016 Sep 25;428(19):3737-51. doi: 10.1016/j.jmb.2016.07.010. Epub 2016 Jul 27.
S-Nitrosylation is well established as an important post-translational regulator in protein function and signaling. However, relatively little is known about its structural and dynamical consequences. We have investigated the effects of S-nitrosylation on the rhodanese domain of the Escherichia coli integral membrane protein YgaP by NMR, X-ray crystallography, and mass spectrometry. The results show that the active cysteine in the rhodanese domain of YgaP is subjected to two competing modifications: S-nitrosylation and S-sulfhydration, which are naturally occurring in vivo. It has been observed that in addition to inhibition of the sulfur transfer activity, S-nitrosylation of the active site residue Cys63 causes an increase in slow motion and a displacement of helix 5 due to a weakening of the interaction between the active site and the helix dipole. These findings provide an example of how nitrosative stress can exert action at the atomic level.
S-亚硝基化作为蛋白质功能和信号传导中一种重要的翻译后调节机制已得到充分证实。然而,关于其结构和动力学后果的了解相对较少。我们通过核磁共振(NMR)、X射线晶体学和质谱法研究了S-亚硝基化对大肠杆菌整合膜蛋白YgaP的硫转移酶结构域的影响。结果表明,YgaP硫转移酶结构域中的活性半胱氨酸会受到两种相互竞争的修饰:S-亚硝基化和S-巯基化,这两种修饰在体内自然发生。据观察,除了抑制硫转移活性外,活性位点残基Cys63的S-亚硝基化还会导致慢运动增加以及由于活性位点与螺旋偶极之间相互作用减弱而导致螺旋5发生位移。这些发现提供了一个亚硝化应激如何在原子水平上发挥作用的例子。