Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors
Structural basis of SNT PTB domain interactions with distinct neurotrophic receptors
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DOI：
10.1016/s1097-2765(05)00087-0
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发表时间：
2000-10-01
期刊：
影响因子：
16
通讯作者：
Zhou, MM
中科院分区：
文献类型：
--
作者：
Dhalluin, C;Yan, KS;Zhou, MM
SNT衔接蛋白将成纤维细胞生长因子受体（FGFR）和神经营养因子受体（TRK）的活化抑制到共同的信号传导靶点。SNT-1磷酸酪氨酸结合（PTB）结构域识别典型NPXpY基序处的活化TRK，并在缺乏酪氨酸或天冬酰胺的区域中与非磷酸化FGFR特异性结合。在这里，使用NMR和突变分析，我们表明，PTB结构域利用不同的氨基酸残基组相互作用与FGFR或TRKs在一个相互排斥的方式。FGFR 1肽包裹在PTB结构域的β夹心结构周围，其结合可能受蛋白质中独特C-末端β链构象变化的调节。我们的研究结果表明SNTs作为分子开关介导神经元分化过程中FGFR和TRK信号之间的重要相互作用的机制。
SNT adaptor proteins transduce activation of fibroblast growth factor receptors (FGFRs) and neurotrophin receptors (TRKs) to common signaling targets. The SNT-1 phosphotyrosine binding (PTB) domain recognizes activated TRKs at a canonical NPXpY motif and, atypically, binds to nonphosphorylated FGFRs in a region lacking tyrosine or asparagine. Here, using NMR and mutational analyses, we show that the PTB domain utilizes distinct sets of amino acid residues to interact with FGFRs or TRKs in a mutually exclusive manner. The FGFR1 peptide wraps around the beta sandwich structure of the PTB domain, and its binding is possibly regulated by conformational change of a unique C-terminal beta strand in the protein. Our results suggest mechanisms by which SNTs serve as molecular switches to mediate the essential interplay between FGFR and TRK signaling during neuronal differentiation.