Activation mechanism of the MAP kinase ERK2 by dual phosphorylation
Activation mechanism of the MAP kinase ERK2 by dual phosphorylation
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DOI：
10.1016/s0092-8674(00)80351-7
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发表时间：
1997-09-05
期刊：
影响因子：
64.5
通讯作者：
Goldsmith, EJ
中科院分区：
文献类型：
--
作者：
Canagarajah, BJ;Khokhlatchev, A;Goldsmith, EJ
MAP激酶ERK 2的活性形式的结构已经被解决，在磷酸化唇内的苏氨酸和酪氨酸残基上磷酸化。唇被重折叠，使磷酸苏氨酸和磷酸酪氨酸与表面富含丝氨酸的结合位点对齐。构象变化发生在唇和邻近结构中，包括P+1位点、MAP激酶插入、C末端延伸和螺旋C。结构域旋转和脯氨酸导向的P+1特异性口袋的重塑是激活的原因。P+1口袋的构象类似于第二个脯氨酸导向的激酶，CDK 2-CyclinA，从而允许定义这种特异性的起源。唇外的构象变化提供了其他细胞成分可以感受到磷酸化状态的位点。
The structure of the active form of the MAP kinase ERK2 has been solved, phosphorylated on a threonine and a tyrosine residue within the phosphorylation lip. The lip is refolded, bringing the phosphothreonine and phosphotyrosine into alignment with surface arginine-rich binding sites. Conformational changes occur in the lip and neighboring structures, including the P+1 site, the MAP kinase insertion, the C-terminal extension, and helix C. Domain rotation and remodeling of the proline-directed P+1 specificity pocket account for the activation. The conformation of the P+1 pocket is similar to a second proline-directed kinase, CDK2-CyclinA, thus permitting the origin of this specificity to be defined. Conformational changes outside the lip provide loci at which the state of phosphorylation can be felt by other cellular components.