Chen H I, Sudol M
Laboratory of Molecular Oncology, Rockefeller University, New York, NY 10021, USA.
Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7819-23. doi: 10.1073/pnas.92.17.7819.
The WW domain has previously been described as a motif of 38 semiconserved residues found in seemingly unrelated proteins, such as dystrophin, Yes-associated protein (YAP), and two transcriptional regulators, Rsp-5 and FE65. The molecular function of the WW domain has been unknown until this time. Using a functional screen of a cDNA expression library, we have identified two putative ligands of the WW domain of YAP, which we named WBP-1 and WBP-2. Peptide sequence comparison between the two partial clones revealed a homologous region consisting of a proline-rich domain followed by a tyrosine residue (with the shared sequence PPPPY), which we shall call the PY motif. Binding assays and site-specific mutagenesis have shown that the PY motif binds with relatively high affinity and specificity to the WW domain of YAP, with the preliminary consensus XPPXY being critical for binding. Herein, we have implicated the WW domain with a role in mediating protein-protein interactions, as a variant of the paradigm set by Src homology 3 domains and their proline-rich ligands.
WW 结构域此前被描述为在看似不相关的蛋白质中发现的由38个半保守残基组成的基序，如肌营养不良蛋白、Yes相关蛋白（YAP）以及两种转录调节因子Rsp-5和FE65。直到现在，WW结构域的分子功能仍不清楚。通过对cDNA表达文库进行功能筛选，我们鉴定出了YAP的WW结构域的两种假定配体，我们将其命名为WBP-1和WBP-2。对这两个部分克隆进行肽序列比较，发现了一个同源区域，该区域由一个富含脯氨酸的结构域和一个酪氨酸残基组成（共有序列为PPPPY），我们将其称为PY基序。结合实验和位点特异性诱变表明，PY基序以相对较高的亲和力和特异性与YAP的WW结构域结合，初步的共有序列XPPXY对结合至关重要。在此，我们认为WW结构域在介导蛋白质-蛋白质相互作用中发挥作用，类似于Src同源3结构域及其富含脯氨酸的配体所设定的模式。
