Syk酪氨酸激酶在信号转导通路中普遍存在的结构基础，是由其调控性SH2域的晶体结构与双磷酸化的ITAM肽结合而成的。,Journal of Molecular Biology

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Syk酪氨酸激酶在信号转导通路中普遍存在的结构基础，是由其调控性SH2域的晶体结构与双磷酸化的ITAM肽结合而成的。
Journal of Molecular Biology ( IF 4.7 ) Pub Date : 1998 Aug 21 , DOI: 10.1006/jmbi.1998.1964
Klaus Fütterer , Jane Wong , Richard A. Grucza , Andrew C. Chan , Gabriel Waksman

由ZAP-70和Syk组成的Syk激酶家族在各种免疫和非免疫细胞中起着重要作用。该激酶家族的特征在于存在两个相邻的SH2结构域，其通过受体编码的酪氨酸磷酸化基序介导其在膜中的定位。尽管这两种激酶具有许多结构和功能特征，但Syk的更普遍的性质表明，该激酶可以容纳更多的基序来介导其功能。我们目前与双磷酸化ITAM肽复合的Syk的串联SH2域的晶体结构。通过3.0 A分辨率的多个同构置换解决了该结构。不对称单元包含六份配体蛋白，在两个SH2域的相对方向上揭示了令人惊讶的灵活性。C-末端磷酸酪氨酸结合位点与ZAP-70的等效区域非常不同，这表明与ZAP-70相比，Syk的两个SH2结构域可以充当独立单元。Syk的SH2模块的构象柔韧性和结构独立性可能为Syk在各种信号转导途径中更普遍的参与提供了分子基础。

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Structural basis for Syk tyrosine kinase ubiquity in signal transduction pathways revealed by the crystal structure of its regulatory SH2 domains bound to a dually phosphorylated ITAM peptide.

The Syk family of kinases, consisting of ZAP-70 and Syk, play essential roles in a variety of immune and non-immune cells. This family of kinases is characterized by the presence of two adjacent SH2 domains which mediate their localization to the membrane through receptor encoded tyrosine phosphorylated motifs. While these two kinases share many structural and functional features, the more ubiquitous nature of Syk has suggested that this kinase may accommodate a greater variety of motifs to mediate its function. We present the crystal structure of the tandem SH2 domain of Syk complexed with a dually phosphorylated ITAM peptide. The structure was solved by multiple isomorphous replacement at 3.0 A resolution. The asymmetric unit comprises six copies of the liganded protein, revealing a surprising flexibility in the relative orientation of the two SH2 domains. The C-terminal phosphotyrosine-binding site is very different from the equivalent region of ZAP-70, suggesting that in contrast to ZAP-70, the two SH2 domains of Syk can function as independent units. The conformational flexibility and structural independence of the SH2 modules of Syk likely provides the molecular basis for the more ubiquitous involvement of Syk in a variety of signal transduction pathways.

更新日期：2017-01-31

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