Regulation of Bin1 SH3 domain binding by phosphoinositides
Regulation of Bin1 SH3 domain binding by phosphoinositides
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DOI：
10.1038/sj.emboj.7600442
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发表时间：
2004-11-10
期刊：
影响因子：
11.4
通讯作者：
Sabe, H
中科院分区：
文献类型：
--
作者：
Kojima, C;Hashimoto, A;Sabe, H
Bin 1/M-amphiphysin-II是一种在成年横纹肌横小管中高度表达的amphiphysin-II亚型，并与其生物发生有关。Bin 1包含一个基本的独特氨基酸序列，外显子10，它与某些磷酸肌醇如磷脂酰肌醇-4，5-二磷酸（PI（4，5）P-2）相互作用，定位于膜。在这里，我们发现外显子10也结合到Bin 1本身的src同源3（SH 3）结构域，因此阻断SH 3结构域与其典型PxxP配体（包括发动蛋白）的结合。通过在体外或在过表达磷脂酰肌醇4-磷酸5-激酶的细胞中加入PI（4，5）P-2，这种阻断被释放。Bin 1 SH 3结构域的外显子10结合界面与其PxxP结合界面大部分重叠。我们还表明，PLC delta pleckstrin同源结构域，另一个PI（4，5）P-2结合模块，不能取代外显子10的Bin 1功能在横小管形成，并建议的双重生化特性的外显子10在肌发生的重要性。我们的研究结果揭示了SH 3结构域调控的一种新机制，并表明SH 3介导的Bin 1的蛋白质-蛋白质相互作用受外显子10的调控，因此只有当Bin 1定位于某些膜下区域时才可能发生。
Bin1/M-amphiphysin-II is an amphiphysin-II isoform highly expressed in transverse tubules of adult striated muscle and is implicated in their biogenesis. Bin1 contains a basic unique amino-acid sequence, Exon10, which interacts with certain phosphoinositides such as phosphatidylinositol-4,5- bisphosphate (PI(4,5) P-2), to localize to membranes. Here we found that Exon10 also binds to the src homology 3 (SH3) domain of Bin1 itself, and hence blocks the binding of the SH3 domain to its canonical PxxP ligands, including dynamin. This blockage was released by addition of PI(4,5) P-2 in vitro or in cells overexpressing phosphatidylinositol 4-phosphate 5-kinase. The Exon10-binding interface of the Bin1 SH3 domain largely overlapped with its PxxP-binding interface. We also show that the PLCdelta pleckstrin homology domain, another PI(4,5) P-2-binding module, cannot substitute for Exon10 in Bin1 function in transverse tubule formation, and suggest the importance of the dual biochemical properties of Exon10 in myogenesis. Our results exemplify a novel mechanism of SH3 domain regulation, and suggest that the SH3-mediated protein - protein interactions of Bin1 are regulated by Exon10 so that it may only occur when Bin1 localizes to certain submembrane areas.