蛋白质动力学在 G 蛋白偶联受体功能中的作用：β2AR 和视紫红质的启示。
The role of protein dynamics in GPCR function: insights from the β2AR and rhodopsin.
机构信息
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA.
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, CA 94305, USA.
出版信息
Curr Opin Cell Biol. 2014 Apr;27:136-43. doi: 10.1016/j.ceb.2014.01.008. Epub 2014 Feb 17.
Abstract
G protein-coupled receptors (GPCRs) are versatile signaling proteins that mediate complex cellular responses to hormones and neurotransmitters. Recent advances in GPCR crystallography have provided inactive and active state structures for rhodopsin and the β2 adrenergic receptor (β2AR). Although these structures suggest a two-state 'on-off' mechanism of receptor activation, other biophysical studies and observed signaling versatility suggest that GPCRs are highly dynamic and exist in a multitude of functionally distinct conformations. To fully understand how GPCRs work, we must characterize these conformations and determine how ligands affect their energetics and rates of interconversion. This brief review will compare and contrast the dynamic properties of rhodopsin and β2AR that shed light on the role of structural dynamics in their distinct signaling behaviors.
摘要
G 蛋白偶联受体（GPCRs）是多功能的信号蛋白，可介导激素和神经递质对细胞的复杂反应。GPCR 晶体学的最新进展为视紫红质和β2 肾上腺素能受体（β2AR）提供了非活性和活性状态的结构。尽管这些结构表明受体激活的“开-关”机制是两态的，但其他生物物理研究和观察到的信号多功能性表明，GPCRs 具有高度的动态性，存在多种功能上不同的构象。为了全面了解 GPCR 如何发挥作用，我们必须描述这些构象，并确定配体如何影响它们的能量和相互转化的速率。这篇简短的综述将比较和对比视紫红质和β2AR 的动态特性，这些特性阐明了结构动力学在它们不同的信号转导行为中的作用。
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