THE WW DOMAIN OF YES-ASSOCIATED PROTEIN BINDS A PROLINE-RICH LIGAND THAT DIFFERS FROM THE CONSENSUS ESTABLISHED FOR SRC HOMOLOGY 3-BINDING MODULES
THE WW DOMAIN OF YES-ASSOCIATED PROTEIN BINDS A PROLINE-RICH LIGAND THAT DIFFERS FROM THE CONSENSUS ESTABLISHED FOR SRC HOMOLOGY 3-BINDING MODULES
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DOI：
10.1073/pnas.92.17.7819
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发表时间：
1995-08-15
影响因子：
11.1
通讯作者：
SUDOL, M
中科院分区：
文献类型：
--
作者：
CHEN, HI;SUDOL, M
此前，WW结构域被描述为一个由38个半保守残基组成的基序，这些残基存在于看似不相关的蛋白质中，如dystrophin、YAP和两个转录调控因子RSP-5和FE65。到目前为止，WW结构域的分子功能一直是未知的。通过对cDNA表达文库的功能筛选，我们已经确定了YAP WW结构域的两个可能的配体，我们将其命名为WBP-1和WBP-2。两个部分克隆的肽序列比较显示了一个同源区，它由一个富含Pro的结构域和一个酪氨酸残基(具有共同的序列PPPPY)组成，我们称之为PY基序。结合分析和定点突变表明，PY基序与YAP的WW结构域具有较高的亲和力和特异性，初步达成的共识XPPXY是结合的关键。在这里，我们暗示了WW结构域在介导蛋白质-蛋白质相互作用中的作用，作为由Src同源3结构域及其富含Pro的配体所设定的范例的变体。
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.