Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains
Arginine methylation inhibits the binding of proline-rich ligands to Src homology 3, but not WW, domains
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DOI：
10.1074/jbc.m909368199
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发表时间：
2000-05-26
影响因子：
4.8
通讯作者：
Richard, S
中科院分区：
文献类型：
--
作者：
Bedford, MT;Frankel, A;Richard, S
已知SRC同源3(SH3)和WW结构域与其各自配体中的富含Pro的基序相关联。在这里，我们证明了所提出的Src激酶适配蛋白Sam68是一个配体，其富含Pro的基序与P59(Fyn)的SH3结构域和磷脂酶C-1的SH3结构域以及FBP30和FBP21的WW结构域相互作用。这些富含脯氨酸的基序的两侧是代表I型蛋白精氨酸N-甲基转移酶靶标的RG重复序列。这些RG重复序列中精氨酸残基的不对称二甲基化显著减少了P59(Fyn)的SH3结构域和磷脂酶C-1的结合，但对它们与FBP30的WW结构域的结合没有影响。这些结果表明，蛋白质精氨酸甲基化可以选择性地调节特定的蛋白质-蛋白质相互作用，并且存在不可逆调节SH3结构域介导的相互作用的机制。
Src homology 3 (SH3) and WW domains are known to associate with proline-rich motifs within their respective ligands. Here we demonstrate that the proposed adapter protein for Src kinases, Sam68, is a ligand whose proline-rich motifs interact with the SH3 domains of p59(fyn) and phospholipase C gamma-1 as well as with the WW domains of FBP30 and FBP21. These proline-rich motifs, in turn, are flanked by RG repeats that represent targets for the type I protein arginine N-methyltransferase. The asymmetrical dimethylation of arginine residues within these RG repeats dramatically reduces the binding of the SH3 domains of p59(fyn) and phospholipase C gamma-1, but has no effect on their binding to the WW domain of FBP30. These results suggest that protein arginine methylation can selectively modulate certain protein-protein interactions and that mechanisms exist for the irreversible regulation of SH3 domain-mediated interactions.