Klappa P, Freedman R B, Langenbuch M, Lan M S, Robinson G K, Ruddock L W
Department of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Biochem J. 2001 Mar 15;354(Pt 3):553-9. doi: 10.1042/0264-6021:3540553.
Using a cross-linking approach, we have recently demonstrated that radiolabelled model peptides or misfolded proteins specifically interact in vitro with two members of the protein disulphide- isomerase family, namely PDI and PDIp, in a crude extract from sheep pancreas microsomes. In addition, we have shown that tyrosine and tryptophan residues within a peptide are the recognition motifs for the binding to PDIp. Here we examine non-peptide ligands and present evidence that a hydroxyaryl group is a structural motif for the binding to PDIp; simple constructs containing this group and certain xenobiotics and phytoestrogens, which contain an unmodified hydroxyaryl group, can all efficiently inhibit peptide binding to PDIp. To our knowledge this is the first time that the recognition motif of a molecular chaperone or folding catalyst has been specified as a simple chemical structure.
通过交联方法，我们最近证明，放射性标记的模型肽或错误折叠的蛋白质在体外与蛋白质二硫键异构酶家族的两个成员，即PDI和PDIp，在绵羊胰腺微粒体的粗提物中特异性相互作用。此外，我们已经表明，肽内的酪氨酸和色氨酸残基是与PDIp结合的识别基序。在这里，我们研究了非肽配体，并提供证据表明羟基芳基是与PDIp结合的结构基序；含有该基团的简单构建体以及某些含有未修饰羟基芳基的外源性物质和植物雌激素，都能有效抑制肽与PDIp的结合。据我们所知，这是首次将分子伴侣或折叠催化剂的识别基序指定为简单的化学结构。
