Solution structure of the inhibitory phosphorylation domain of myosin phosphatase targeting subunit 1.
Solution structure of the inhibitory phosphorylation domain of myosin phosphatase targeting subunit 1.
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DOI：
10.1002/prot.22529
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发表时间：
2009-11-15
影响因子：
2.9
通讯作者：
Ohki, Shin-ya
中科院分区：
文献类型：
--
作者：
Mori, Shunsuke;Iwaoka, Ryou;Eto, Masumi;Ohki, Shin-ya
细胞运动，如平滑肌收缩和细胞迁移，是由肌球蛋白II和其他细胞骨架蛋白调控轻链的可逆磷酸化控制的。越来越多的证据表明，在脊椎动物的平滑肌细胞和其他类型的细胞中，肌球蛋白磷酸酶（myosin phosphatase， MP）在控制肌球蛋白II以及其他细胞骨架蛋白（包括ezrin、moesin和radixin）的磷酸化中起着重要作用。1mp是一种全酶，由1型丝氨酸/苏氨酸磷酸酶(PP1C) δ异构体的催化亚基、肌球蛋白磷酸酶靶向亚基1 （MYPT1）和辅助亚基M21组成。在这个三元复合物中，MYPT1负责调节磷酸酶活性。最近的x射线晶体学研究揭示了PP1C与MYPT1的n端锚蛋白重复结构域之间的变构相互作用，这赋予了该酶的底物特异性。当MYPT1的Thr696或Thr853被各种激酶（如ROCK、ZIPK、ILK和PAK）磷酸化时，MP活性被抑制。然而，目前尚不清楚MYPT1的磷酸化如何抑制MP活性。MYPT1 Thr696附近的氨基酸序列在包括MYPT2和MBS85在内的MYPT1家族成员中高度保守。因此，对MYPT1抑制域的结构洞察有望为充分阐明通过磷酸化MYPT1或参与细胞骨架调节中激酶磷酸酶串扰的其他家族成员来控制磷酸酶活性的机制提供新的线索。
Cell motility, such as smooth muscle contraction and cell migration, is controlled by the reversible phosphorylation of the regulatory light chain of myosin II and other cytoskeletal proteins. Mounting evidence suggests that in smooth muscle cells and other types of cells in vertebrates, myosin phosphatase (MP) plays an important role in controlling the phosphorylation of myosin II as well as other cytoskeletal proteins, including ezrin, moesin, and radixin. 1 MP is a holoenzyme consisting of a catalytic subunit of a type-1 Ser/Thr phosphatase (PP1C) delta isoform, a myosin phosphatase targeting subunit 1 (MYPT1), and an accessory subunit M21. In this ternary complex, MYPT1 is responsible for regulating the phosphatase activity. 1A recent X-ray crystallographic study revealed an allosteric interaction between PP1C and the N-terminal ankyrin repeat domain of MYPT1 that confers the substrate specificity of the enzyme. 2 MP activity is suppressed when Thr696 or Thr853 of MYPT1 is phosphorylated by various kinases, such as ROCK, ZIPK, ILK, and PAK. 1, 3 However, it is still unclear how the phosphorylation of MYPT1 inhibits MP activity. The amino acid sequence around Thr696 of MYPT1 is highly conserved among MYPT1 family members including MYPT2 and MBS85. Therefore, structural insights into the inhibitory domain of MYPT1 are expected to provide new clues to fully elucidate the mechanism that controls phosphatase activity via the phosphorylation of MYPT1 or other family members involved in kinasephosphatase crosstalk in cytoskeletal regulation.
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影响因子：
2.7
作者：
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通讯作者：
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影响因子：
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