Scaffold proteins as dynamic integrators of biological processes.
Scaffold proteins as dynamic integrators of biological processes.
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DOI：
10.1016/j.jbc.2022.102628
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发表时间：
2022-12
影响因子：
4.8
通讯作者：
Gilmore, Thomas D.
中科院分区：
文献类型：
--
作者：
DiRusso, Christopher J.;Dashtiahangar, Maryam;Gilmore, Thomas D.
支架蛋白作为多个蛋白质对接的分子枢纽，组织有效的功能单位进行信号级联。超过300个人类蛋白质被描述为支架，作用于不同的信号通路。虽然支架这个术语意味着一个静态的、支持性的平台，但现在很清楚的是，支架不是简单的惰性对接站，而是可以经历影响其依赖的信号通路的构象变化。在这篇综述中，我们对已被证明经历了可操作的构象变化的支架蛋白进行了分类，重点介绍了构象变化在经典的酵母支架STE5的活性中所起的作用，以及三种人类支架蛋白(KSR，NEMO，SHANK3)，它们是众所周知的信号通路(RAS，NF-κB，突触后密度)的组成部分。我们还讨论了支架蛋白在液-液相分离过程中的构象变化。支架结构的变化也与人类疾病有关，我们讨论了异常构象变化如何参与与疾病相关的支架和信号功能的失调。最后，我们讨论了了解这些构象动力学将如何提供对信号级联的灵活性的洞察，并可能增强我们治疗支架相关疾病的能力。
Scaffold proteins act as molecular hubs for the docking of multiple proteins to organize efficient functional units for signaling cascades. Over 300 human proteins have been characterized as scaffolds, acting in a variety of signaling pathways. While the term scaffold implies a static, supportive platform, it is now clear that scaffolds are not simply inert docking stations but can undergo conformational changes that affect their dependent signaling pathways. In this review, we catalog scaffold proteins that have been shown to undergo actionable conformational changes, with a focus on the role that conformational change plays in the activity of the classic yeast scaffold STE5, as well as three human scaffold proteins (KSR, NEMO, SHANK3) that are integral to well-known signaling pathways (RAS, NF-κB, postsynaptic density). We also discuss scaffold protein conformational changes vis-à-vis liquid–liquid phase separation. Changes in scaffold structure have also been implicated in human disease, and we discuss how aberrant conformational changes may be involved in disease-related dysregulation of scaffold and signaling functions. Finally, we discuss how understanding these conformational dynamics will provide insight into the flexibility of signaling cascades and may enhance our ability to treat scaffold-associated diseases.
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DOI：
10.1042/bj20140606
发表时间：
2014-12-01
期刊：
The Biochemical journal
影响因子：
--
作者：
Abdul Azeez KR;Knapp S;Fernandes JM;Klussmann E;Elkins JM
通讯作者：
Elkins JM
影响因子：
6.2
作者：
Bozdagi O;Sakurai T;Papapetrou D;Wang X;Dickstein DL;Takahashi N;Kajiwara Y;Yang M;Katz AM;Scattoni ML;Harris MJ;Saxena R;Silverman JL;Crawley JN;Zhou Q;Hof PR;Buxbaum JD
通讯作者：
Buxbaum JD
影响因子：
4.8
作者：
Baisamy, Laurent;Cavin, Sabrina;Diviani, Dario
通讯作者：
Diviani, Dario
影响因子：
16.8
作者：
Bonsor, Daniel A.;Alexander, Patrick;Snead, Kelly;Hartig, Nicole;Drew, Matthew;Messing, Simon;Finci, Lorenzo, I;Nissley, Dwight, V;McCormick, Frank;Esposito, Dominic;Rodriguez-Viciana, Pablo;Stephen, Andrew G.;Simanshu, Dhirendra K.
通讯作者：
Simanshu, Dhirendra K.
影响因子：
64.8
作者：
Brennan, Damian F.;Dar, Arvin C.;Barford, David
通讯作者：
Barford, David