Piecing it together: Unraveling the elusive structure-function relationship in single-pass membrane receptors.
Piecing it together: Unraveling the elusive structure-function relationship in single-pass membrane receptors.
复制标题
DOI：
10.1016/j.bbamem.2017.01.016
复制
发表时间：
2017-09
期刊：
影响因子：
--
通讯作者：
Sachs JN
中科院分区：
文献类型：
--
作者：
Valley CC;Lewis AK;Sachs JN
单通道质膜受体结晶的挑战仍然是理解连接细胞外配体结合和细胞质活化的结构机制的障碍。例如，受体寡聚化和构象动力学之间的复杂相互作用，在历史上，只能从孤立的受体结构域的静态结构中推断出来。因此，膜受体生物学领域的一个基本挑战是将全长受体的实验观察动态（例如扩散和构象灵活性）整合到不同域的静态结构模型中。在某些受体家族中，例如ErbB受体，结构在某种程度上线性地导致了一个假定的激活模型。在其他家族中，例如肿瘤坏死因子（TNF）受体，其结构产生了不同的激活和转导假设机制。在这里，我们详细讨论了这些和其他相关受体，目的是阐明当前建立单通道受体激活综合模型的挑战和机遇。最近，新的实验和计算工具加速了对这些受体的深入理解，这些实验和计算工具提供了结构和动力学的正交视角。因此，这篇综述的目的是在强调受体结构域之间优雅而复杂的构象通信的同时，将这些技术发展置于背景下。这篇文章是Kalina Hristova编辑的题为“细胞膜中膜受体之间的相互作用”的特刊的一部分。
The challenge of crystallizing single-pass plasma membrane receptors has remained an obstacle to understanding the structural mechanisms that connect extracellular ligand binding to cytosolic activation. For example, the complex interplay between receptor oligomerization and conformational dynamics has been, historically, only inferred from static structures of isolated receptor domains. A fundamental challenge in the field of membrane receptor biology, then, has been to integrate experimentally observable dynamics of full-length receptors (e.g. diffusion and conformational flexibility) into static structural models of the disparate domains. In certain receptor families, e.g. the ErbB receptors, structures have led somewhat linearly to a putative model of activation. In other families, e.g. the tumor necrosis factor (TNF) receptors, structures have produced divergent hypothetical mechanisms of activation and transduction. Here, we discuss in detail these and other related receptors, with the goal of illuminating the current challenges and opportunities in building comprehensive models of single-pass receptor activation. The deepening understanding of these receptors has recently been accelerated by new experimental and computational tools that offer orthogonal perspectives on both structure and dynamics. As such, this review aims to contextualize those technological developments as we highlight the elegant and complex conformational communication between receptor domains. This article is part of a Special Issue entitled: Interactions between membrane receptors in cellular membranes edited by Kalina Hristova.
影响因子：
6.8
作者：
Pope CR;Unger VM
通讯作者：
Unger VM