Department of Biochemistry, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390-8816, USA.
Structure. 2010 Dec 8;18(12):1571-8. doi: 10.1016/j.str.2010.09.015.
MAPKs engage substrates, MAP2Ks, and phosphatases via a docking groove in the C-terminal domain of the kinase. Prior crystallographic studies on the unphosphorylated MAPKs p38α and ERK2 defined the docking groove and revealed long-range conformational changes affecting the activation loop and active site of the kinase induced by peptide. Solution NMR data presented here for unphosphorylated p38α with a MEK3b-derived peptide (p38α/pepMEK3b) validate these findings. Crystallograhic data from doubly phosphorylated active p38α (p38α/T∗GY∗/pepMEK3b) reveal a structure similar to unphosphorylated p38α/MEK3b, and distinct from phosphorylated p38γ (p38γ/T∗GY∗) and ERK2 (ERK2/T∗EY∗). The structure supports the idea that MAP kinases adopt three distinct conformations: unphosphorylated, phosphorylated, and a docking peptide-induced form.
MAPKs 通过激酶 C 端结构域中的对接沟与底物、MAP2Ks 和磷酸酶结合。先前对未磷酸化的 MAPKs p38α 和 ERK2 的晶体学研究定义了对接沟，并揭示了由肽诱导的影响激酶激活环和活性位点的长程构象变化。这里为未磷酸化的 p38α 与 MEK3b 衍生肽（p38α/pepMEK3b）提供的溶液 NMR 数据验证了这些发现。来自双磷酸化活性 p38α（p38α/T∗GY∗/pepMEK3b）的晶体学数据揭示了一种与未磷酸化的 p38α/MEK3b 相似的结构，与磷酸化的 p38γ（p38γ/T∗GY∗）和 ERK2（ERK2/T∗EY∗）不同。该结构支持了 MAP 激酶采用三种不同构象的观点：未磷酸化、磷酸化和对接肽诱导的构象。
