Kay B K, Williamson M P, Sudol M
Department of Pharmacology, University of Wisconsin-Madison, Madison, Wisconsin 53706-1532, USA.
FASEB J. 2000 Feb;14(2):231-41.
Acommon focus among molecular and cellular biologists is the identification of proteins that interact with each other. Yeast two-hybrid, cDNA expression library screening, and coimmunoprecipitation experiments are powerful methods for identifying novel proteins that bind to one's favorite protein for the purpose of learning more regarding its cellular function. These same techniques, coupled with truncation and mutagenesis experiments, have been used to define the region of interaction between pairs of proteins. One conclusion from this work is that many interactions occur over short regions, often less than 10 amino acids in length within one protein. For example, mapping studies and 3-dimensional analyses of antigen-antibody interactions have revealed that epitopes are typically 4-7 residues long (1). Other examples include protein-interaction modules, such as Src homology (SH) 2 and 3 domains, phosphotyrosine binding domains (PTB), postsynaptic density/disc-large/ZO1 (PDZ) domains, WW domains, Eps15 homology (EH) domains, and 14-3-3 proteins that typically recognize linear regions of 3-9 amino acids. Each of these domains has been the subject of recent reviews published elsewhere (2 3 4 5 6 7). Among the primary structures of many ligands for protein-protein interactions, the amino acid proline is critical. In particular, SH3, WW, and several new protein-interaction domains prefer ligand sequences that are proline-rich. In addition, even though ligands for EH domains and 14-3-3 domains are not proline-rich, they do include a single proline residue. This review highlights the analysis of those protein-protein interactions that involve proline residues, the biochemistry of proline, and current drug discovery efforts based on proline peptidomimetics.-Kay, B. K., Williamson, M. P., Sudol, M. The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains.
分子和细胞生物学家的一个共同关注点是鉴定相互作用的蛋白质。酵母双杂交、cDNA表达文库筛选和免疫共沉淀实验是鉴定与感兴趣蛋白质结合的新蛋白质的有力方法，目的是更多地了解其细胞功能。这些相同的技术，再加上截短和诱变实验，已被用于确定蛋白质对之间的相互作用区域。这项工作得出的一个结论是，许多相互作用发生在短区域，通常在一种蛋白质内长度小于10个氨基酸。例如，抗原-抗体相互作用的图谱研究和三维分析表明，表位通常长4-7个残基(1)。其他例子包括蛋白质相互作用模块，如Src同源(SH)2和3结构域、磷酸酪氨酸结合结构域(PTB)、突触后密度/盘状大/ZO1(PDZ)结构域、WW结构域、Eps15同源(EH)结构域和14-3-3蛋白，它们通常识别3-9个氨基酸的线性区域。这些结构域中的每一个都是其他地方最近发表的综述的主题(2、3、4、5、6、7)。在许多蛋白质-蛋白质相互作用配体的一级结构中，氨基酸脯氨酸至关重要。特别是，SH3、WW和几个新的蛋白质相互作用结构域更喜欢富含脯氨酸的配体序列。此外，尽管EH结构域和14-3-3结构域的配体不是富含脯氨酸的，但它们确实包含一个脯氨酸残基。本综述重点分析了涉及脯氨酸残基的蛋白质-蛋白质相互作用、脯氨酸的生物化学以及基于脯氨酸肽模拟物的当前药物发现工作。-凯，B.K.，威廉姆森，M.P.，苏多尔，M.脯氨酸的重要性：信号蛋白中富含脯氨酸的基序与其同源结构域的相互作用。
