Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition
Crystal structures of the XLP protein SAP reveal a class of SH2 domains with extended, phosphotyrosine-independent sequence recognition
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DOI：
10.1016/s1097-2765(00)80206-3
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发表时间：
1999-10-01
期刊：
影响因子：
16
通讯作者：
Eck, MJ
中科院分区：
文献类型：
--
作者：
Poy, F;Yaffe, MB;Eck, MJ
SAP是X连锁淋巴组织增生综合征（XLP）中基因突变的产物，由单个SH 2结构域组成，已证明该结构域可结合淋巴细胞辅助受体SLAM的胞质尾部。在这里，我们描述的结构表明，SAP结合磷酸化和非磷酸化的SLAM肽在一个类似的模式，与酪氨酸或磷酸酪氨酸残基插入到磷酸酪氨酸结合口袋。我们发现，具体的相互作用与残基的N-末端的酪氨酸，除了更多的特征C-末端的相互作用，稳定的复合物。在XLP患者中鉴定的磷酸肽文库筛选和突变分析证实，这些延长的相互作用是SAP功能所需的。此外，我们表明，SAP和类似的蛋白质EAT-2识别的序列基序TlpYXX（V/I）。
SAP, the product of the gene mutated in X-linked lymphoproliferative syndrome (XLP), consists of a single SH2 domain that has been shown to bind the cytoplasmic tail of the lymphocyte coreceptor SLAM. Here we describe structures that show that SAP binds phosphorylated and nonphosphorylated SLAM peptides in a similar mode, with the tyrosine or phosphotyrosine residue inserted into the phosphotyrosine-binding pocket. We find that specific interactions with residues N-terminal to the tyrosine, in addition to more characteristic C-terminal interactions, stabilize the complexes. A phosphopeptide library screen and analysis of mutations identified in XLP patients confirm that these extended interactions are required for SAP function. Further, we show that SAP and the similar protein EAT-2 recognize the sequence motif TlpYXX(V/I).