The Third Conformation of p38α MAP Kinase Observed in Phosphorylated p38α and in Solution

被引：26

作者：

Akella, Radha ^{[1
]}

Min, Xiaoshan ^{[1
]}

Wu, Qiong ^{[1
]}

Gardner, Kevin H. ^{[1
]}

Goldsmith, Elizabeth J. ^{[1
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA

来源：

STRUCTURE | 2010年 / 18卷 / 12期

关键词：

ACTIVATED PROTEIN-KINASES; DOCKING INTERACTIONS; STRUCTURAL BASIS; SUBSTRATE-SPECIFICITY; BINDING-SITE; P38; PATHWAY; MOTIF; ERK2; DETERMINANTS; LOOP;

D O I：

10.1016/j.str.2010.09.015

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 p38 alpha 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 p38 alpha with a MEK3b-derived peptide (p38 alpha/pepMEK3b) validate these findings. Crystallograhic data from doubly phosphorylated active p38 alpha (p38 alpha/T(star)GY(star)/pepMEK3b) reveal a structure similar to unphosphorylated p38 alpha/MEK3b, and distinct from phosphorylated p38 gamma (p38 gamma/T(star)GY(star)) and ERK2 (ERK2/(TEY star)-E-star). The structure supports the idea that MAP kinases adopt three distinct conformations: unphosphorylated, phosphorylated, and a docking peptide-induced form.

引用

页码：1571 / 1578

页数：8

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