排斥导向分子 (RGM) -新原蛋白信号枢纽的结构
Christian H Bell1, Eleanor Healey1, Susan van Erp2
1Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK.
Science (New York, N.Y.)
|June 8, 2013
概括
排斥导向分子家族成员 (RGMs) 通过新原蛋白 (NEO1) 通过一种保存的结构机制发出信号. 这项研究揭示了RGMB蛋白折叠及其与NEO1的相互作用,解释了RGM介导的细胞过程.
科学领域:
- 分子生物学分子生物学
- 结构生物学 结构生物学
- 细胞生物学 细胞生物学
背景情况:
- 排斥导向分子家族成员 (RGMs) 是细胞功能的关键调节者,包括细胞运动性,粘附性,免疫反应和铁代谢.
- 通过RGMs通过它们的受体新生素 (NEO1) 启动信号传递的精确机制在很大程度上仍未被描述.
研究的目的:
- 阐明RGM-NEO1复合体形成和信号启动的结构基础.
- 描述RGMB (龙) 的结构及其与NEO1.1的相互作用.
主要方法:
- 采用X射线晶体学来确定NEO1 RGM结合区域和NEO1-RGMB复合物的结构.
- 生物化学测试被用来调查观察到的结构和机制的功能影响.
主要成果:
- RGMB的晶体结构揭示了一种新的蛋白质折叠和一种对RGM功能至关重要的自催化裂解机制.
- NEO1-RGMB复合体的结构表明,RGMB外域基因以pH依赖的方式稳定NEO1受体.
- 这种RGM-NEO1复杂架构在不同的RGM家族成员中得到保存,表明了一个共同的信号机制.
结论:
- 这些发现为了解RGM如何通过NEO1.1启动信号提供了一个结构框架.
- 确定了RGM-NEO1复合体的保存架构是RGMs调节的多个信号通路的基础.
- 这项工作提供了对RGM与疾病相关的突变以及潜在的治疗策略的见解.
相关概念视频
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Interaction domains in cell signaling
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Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
01:14Rab Proteins
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
01:24Small GTPases - Ras and Rho
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Three regulatory proteins control their activity:
Three regulatory proteins control their activity:
01:22Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
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03:14Notch Signaling Pathway
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...