Phosphorylation mechanism and structure of serine-arginine protein kinases.
Phosphorylation mechanism and structure of serine-arginine protein kinases.
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DOI：
10.1111/j.1742-4658.2010.07992.x
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发表时间：
2011-02
期刊：
影响因子：
--
通讯作者：
Adams JA
中科院分区：
文献类型：
--
作者：
Ghosh G;Adams JA
mRNA的剪接需要一组称为SR蛋白的必需因子，其参与剪接体的成熟。这些蛋白质含有一个或两个RNA识别结构域（RRM）和一个富含Arg-Ser重复序列的C-末端结构域（RS结构域）。SR蛋白在RS结构域中的许多丝氨酸处被SRPK蛋白激酶家族磷酸化。RS结构域磷酸化是SR蛋白进入细胞核所必需的，并且在选择性剪接、mRNA输出和其他加工事件中也可能起重要作用。虽然SR蛋白在体内被多磷酸化，但这种复杂反应的机制最近才被阐明。SRSF 1是SR蛋白家族的原型，被SRPK 1区域特异性磷酸化，SRPK 1是一种控制细胞质-核定位的翻译后修饰。SRPK 1以异常高的亲和力结合SRSF 1，并使用结合顺序的C至N磷酸化和几个进行性步骤的机制快速修饰RS结构域（RS 1）的N-末端部分中的约10-12个丝氨酸。SRPK 1采用高度动态的进料机制进行RS结构域磷酸化，其中RS 1的N-末端部分最初结合到激酶结构域的大叶中的对接槽。在随后的几轮磷酸化中，该N-末端片段易位到活性位点，RRM 2中的β链展开并占据对接槽。这些研究表明，有效的区域特异性磷酸化的SRSF 1是一个轮廓的结合腔SRPK 1，在RS结构域中的一个冗长的Arg-Ser重复片段和高度定向加工机制的结果。
The splicing of mRNA requires a group of essential factors known as SR proteins that participate in the maturation of the spliceosome. These proteins contain one or two RNA recognition domains (RRMs) and a C-terminal domain rich in Arg-Ser repeats (RS domain). SR proteins are phosphorylated at numerous serines in the RS domain by the SRPK family of protein kinases. RS domain phosphorylation is necessary for entry of SR proteins into the nucleus and may also play important roles in alternative splicing, mRNA export and other processing events. Although SR proteins are polyphosphorylated in vivo, the mechanism underlying this complex reaction has only been recently elucidated. SRSF1, a prototype for the SR protein family, is regiospecifically phosphorylated by SRPK1, a posttranslational modification that controls cytoplasmic-nuclear localization. SRPK1 binds SRSF1 with unusually high affinity and rapidly modifies about 10–12 serines in the N-terminal portion of the RS domain (RS1) using a mechanism that incorporates sequential, C-to-N phosphorylation and several processive steps. SRPK1 employs a highly dynamic feeding mechanism for RS domain phosphorylation in which the N-terminal portion of RS1 is initially bound to a docking groove in the large lobe of the kinase domain. Upon subsequent rounds of phosphorylation, this N-terminal segment translocates into the active site and a β strand in RRM2 unfolds and occupies the docking groove. These studies indicate that efficient regiospecific phosphorylation of SRSF1 is the result of a contoured binding cavity in SRPK1, a lengthy Arg-Ser repetitive segment in the RS domain and a highly directional processing mechanism.
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影响因子：
14.9
作者：
Haynes C;Iakoucheva LM
通讯作者：
Iakoucheva LM
DOI：
10.1016/j.str.2008.12.023
发表时间：
2009-03-11
期刊：
Structure (London, England : 1993)
影响因子：
--
作者：
Bullock AN;Das S;Debreczeni JE;Rellos P;Fedorov O;Niesen FH;Guo K;Papagrigoriou E;Amos AL;Cho S;Turk BE;Ghosh G;Knapp S
通讯作者：
Knapp S
影响因子：
11.4
作者：
Hubbard, SR
通讯作者：
Hubbard, SR
影响因子：
4.8
作者：
DUNCAN, PI;HOWELL, BW;BELL, JC
通讯作者：
BELL, JC
影响因子：
2.9
作者：
Huynh, Nhat;Ma, Chen-Ting;Ghosh, Gourisankar
通讯作者：
Ghosh, Gourisankar