胰岛素受体的激活机制:一个结构视角。

IF 12.1 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Eunhee Choi, Xiao-Chen Bai
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引用次数: 6

摘要

胰岛素受体(IR)是一种II型受体酪氨酸激酶,在代谢、生长和增殖中起重要作用。IR信号的失调与许多人类疾病有关,如糖尿病和癌症。近年来,冷冻电子显微镜的分辨率革命导致了几种具有不同数量的胰岛素结合分子的IR结构的确定,这极大地提高了我们对胰岛素如何激活IR的理解。在这里,我们回顾了胰岛素诱导的IR激活机制,包括(a)胰岛素在位点1和位点2的详细结合模式和功能,以及(b)胰岛素诱导的IR激活所需的结构转变。我们强调了IR信号的激活和调节的其他几个关键方面,并讨论了我们对IR激活机制和未来研究的潜在途径的理解中的剩余空白。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The Activation Mechanism of the Insulin Receptor: A Structural Perspective.

The insulin receptor (IR) is a type II receptor tyrosine kinase that plays essential roles in metabolism, growth, and proliferation. Dysregulation of IR signaling is linked to many human diseases, such as diabetes and cancers. The resolution revolution in cryo-electron microscopy has led to the determination of several structures of IR with different numbers of bound insulin molecules in recent years, which have tremendously improved our understanding of how IR is activated by insulin. Here, we review the insulin-induced activation mechanism of IR, including (a) the detailed binding modes and functions of insulin at site 1 and site 2 and (b) the insulin-induced structural transitions that are required for IR activation. We highlight several other key aspects of the activation and regulation of IR signaling and discuss the remaining gaps in our understanding of the IR activation mechanism and potential avenues of future research.

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来源期刊
Annual review of biochemistry
Annual review of biochemistry 生物-生化与分子生物学
CiteScore
33.90
自引率
0.00%
发文量
31
期刊介绍: The Annual Review of Biochemistry, in publication since 1932, sets the standard for review articles in biological chemistry and molecular biology. Since its inception, these volumes have served as an indispensable resource for both the practicing biochemist and students of biochemistry.
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