Zhou M M, Huang B, Olejniczak E T, Meadows R P, Shuker S B, Miyazaki M, Trüb T, Shoelson S E, Fesik S W
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, Illinois 60064, USA.
Nat Struct Biol. 1996 Apr;3(4):388-93. doi: 10.1038/nsb0496-388.
We present the NMR structure of the PTB domain of insulin receptor substrate-1 (IRS-1) complexed to a tyrosine-phosphorylated peptide derived from the IL-4 receptor. Despite the lack of sequence homology and different binding specificity, the overall fold of the protein is similar to that of the Shc PTB domain and closely resembles that of PH domains. However, the PTB domain of IRS-1 is smaller than that of Shc (110 versus 170 residues) and binds to phosphopeptides in a distinct manner. We explain the phosphopeptide binding specificity based on the structure of the complex and results of site-directed mutagenesis experiments.
我们展示了胰岛素受体底物-1（IRS-1）的PTB结构域与源自白细胞介素-4受体的酪氨酸磷酸化肽复合后的核磁共振结构。尽管缺乏序列同源性且结合特异性不同，但该蛋白的整体折叠与Shc PTB结构域相似，且与PH结构域极为相像。然而，IRS-1的PTB结构域比Shc的PTB结构域小（分别为110个和170个残基），并且以独特的方式结合磷酸肽。我们基于复合物的结构和定点诱变实验结果解释了磷酸肽的结合特异性。
