Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb
Multiple modes of peptide recognition by the PTB domain of the cell fate determinant Numb
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DOI：
10.1093/emboj/19.7.1505
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发表时间：
2000-04-03
期刊：
影响因子：
11.4
通讯作者：
Forman-Kay, JD
中科院分区：
文献类型：
--
作者：
Zwahlen, C;Li, SC;Forman-Kay, JD
细胞命运决定子Numb的磷酸酪氨酸结合（PTB）结构域参与体内多种蛋白质复合物的形成，并可在体外结合多种肽序列。为了研究这种蛋白质模块的混杂性质的结构基础，我们已经确定了它的溶液结构，通过NMR在一个复杂的肽含有来自Numb相关激酶（Nak）的匪SF序列。发现Nak肽采用与先前确定的含有GPpY序列的肽显著不同的结构。与GPpY肽采用的螺旋转角相反，Nak肽在匪SF位点形成β转角，然后在C末端附近形成另一转角。Numb PTB结构域似乎通过接合蛋白质的结合表面的不同量来识别在一级和二级结构两者中不同的肽。我们的研究结果表明，通过一个单一的PTB结构域可能与多个不同的靶蛋白相互作用，以控制一个复杂的生物过程，如不对称细胞分裂的机制。
The phosphotyrosine-binding (PTB) domain of the cell fate determinant Numb is involved in the formation of multiple protein complexes in vivo and can bind a diverse array of peptide sequences in vitro. To investigate the structural basis for the promiscuous nature of this protein module, we have determined its solution structure by NMR in a complex with a peptide containing an NMSF sequence derived from the Numb-associated kinase (Nak). The Nak peptide was found to adopt a significantly different structure from that of a GPpY sequence-containing peptide previously determined. In contrast to the helical turn adopted by the GPpY peptide, the Nak peptide forms a beta-turn at the NMSF site followed by another turn near the C-terminus. The Numb PTB domain appears to recognize peptides that differ in both primary and secondary structures by engaging various amounts of the binding surface of the protein. Our results suggest a mechanism through which a single PTB domain might interact with multiple distinct target proteins to control a complex biological process such as asymmetric cell division.