CNRS UMR 5048, Centre de Biochimie Structurale, 29, rue de Navacelles 34090 Montpellier, France.
Structure. 2011 Oct 12;19(10):1525-34. doi: 10.1016/j.str.2011.07.011.
The protein Rv0020c from Mycobacterium tuberculosis, also called FhaA, is one of the major substrates of the essential Ser/Thr protein kinase (STPK) PknB. The protein is composed of three domains and is phosphorylated on a unique site in its N terminus. We solved the solution structure of both N- and C-terminal domains and demonstrated that the approximately 300 amino acids of the intermediate domain are not folded. We present evidence that the FHA, a phosphospecific binding domain, of Rv0020c does not interact with the phosphorylated catalytic domains of PknB, but with the phosphorylated juxtamembrane domain that links the catalytic domain to the mycobacterial membrane. We also demonstrated that the degree and the pattern of phosphorylation of this juxtamembrane domain modulates the affinity of the substrate (Rv0020c) toward its kinase (PknB).
结核分枝杆菌蛋白 Rv0020c，也称为 FhaA，是必需丝氨酸/苏氨酸蛋白激酶（STPK）PknB 的主要底物之一。该蛋白由三个结构域组成，其 N 末端有一个独特的磷酸化位点。我们解析了该蛋白的 N 端和 C 端结构域的溶液结构，并证实中间结构域的大约 300 个氨基酸不折叠。我们提供的证据表明，Rv0020c 的 FHA（一种磷酸化特异性结合域）不与 PknB 的磷酸化催化结构域相互作用，而是与连接催化结构域和分枝杆菌膜的磷酸化跨膜结构域相互作用。我们还证明，这个跨膜结构域的磷酸化程度和模式调节了底物（Rv0020c）对其激酶（PknB）的亲和力。
