Goethe-University Frankfurt am Main, Institute for Organic Chemistry and Chemical Biology, Centre for Biomolecular Magnetic Resonance (BMRZ), Frankfurt am Main, Germany.
Goethe-University Frankfurt am Main, Institute of Biochemistry, Biocenter, Frankfurt am Main, Germany.
FEBS Lett. 2018 Apr;592(7):1233-1245. doi: 10.1002/1873-3468.13022. Epub 2018 Mar 25.
Although intrinsically disordered proteins or protein domains (IDPs or IDD) are less abundant in bacteria than in eukaryotes, their presence in pathogenic bacterial proteins is important for protein-protein interactions. The protein tyrosine kinase A (PtkA) from Mycobacterium tuberculosis possesses an 80-residue disordered region (IDD ) of unknown function, located N-terminally to the well-folded kinase core domain. Here, we characterize the conformation of IDD under varying biophysical conditions and phosphorylation using NMR-spectroscopy. Our results confirm that the N-terminal domain of PtkA exists as an IDD at physiological pH. Furthermore, phosphorylation of IDD increases the activity of PtkA. Our findings will complement future approaches in understanding molecular mechanisms of key proteins in pathogenic virulence.
虽然在细菌中，无序蛋白质或蛋白质结构域（IDPs 或 IDD）的丰度低于真核生物，但它们在致病细菌蛋白质中的存在对于蛋白质-蛋白质相互作用很重要。结核分枝杆菌中的蛋白酪氨酸激酶 A（PtkA）具有一个 80 个残基的无序区域（IDD），其功能未知，位于折叠良好的激酶核心结构域的 N 端。在这里，我们使用 NMR 光谱法在不同的生物物理条件和磷酸化条件下对 IDD 的构象进行了表征。我们的结果证实，PtkA 的 N 端结构域在生理 pH 值下以 IDD 的形式存在。此外，IDD 的磷酸化会增加 PtkA 的活性。我们的发现将补充未来研究致病毒力关键蛋白分子机制的方法。
