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首页> 外文期刊>EMBO Journal >A unique set of SH3-SH3 interactions controls IB1 homodimerization
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A unique set of SH3-SH3 interactions controls IB1 homodimerization

机译：一组独特的SH3-SH3 IB1交互控制homodimerization

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摘要

Islet-brain 1 (IB1 or JIP-1) is a scaffold protein that interacts with components of the c-Jun N-terminal kinase (JNK) signal-transduction pathway. IB1 is expressed at high levels in neurons and in pancreatic beta-cells, where it controls expression of several insulin-secretory components and secretion. IB1 has been shown to homodimerize, but neither the molecular mechanisms nor the function of dimerization have yet been characterized. Here, we show that IB1 homodimerizes through a novel and unique set of Src homology 3 (SH3)-SH3 interactions. X-ray crystallography studies show that the dimer interface covers a region usually engaged in PxxP-mediated ligand recognition, even though the IB1 SH3 domain lacks this motif. The highly stable IB1 homodimer can be significantly destabilized in vitro by three individual point mutations directed against key residues involved in dimerization. Each mutation reduces IB1-dependent basal JNK activity in 293T cells. Impaired dimerization also results in a reduction in glucose transporter type 2 expression and in glucose-dependent insulin secretion in pancreatic beta-cells. Taken together, these results indicate that IB1 homodimerization through its SH3 domain has pleiotropic effects including regulation of the insulin secretion process.
机译：Islet-brain 1 (IB1或JIP-1)是一个脚手架蛋白c-Jun与组件交互氨基端激酶(物)信号转导途径。在胰岛细胞神经元和它控制几个insulin-secretory的表达式组件和分泌。结伴,但无论是分子机制和二聚作用的功能没有特点。通过新颖独特的结伴Src同源性3 (SH3) SH3交互。晶体学研究表明,二聚体接口通常覆盖一个地区从事PxxP-mediated配体识别,即使IB1 SH3领域缺乏这一主题。稳定IB1为显著非稳定的体外由三个个人观点针对关键残基突变二聚作用。在293 t细胞IB1-dependent基底物活动。二聚作用也导致减少受损在葡萄糖转运体和2型表达式glucose-dependent胰腺的胰岛素分泌细胞。表明IB1 homodimerization通过它SH3域包括有多效性的影响调节胰岛素分泌过程。

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