趋化受体和信号传导。

Aaron F Miller, Joseph J Falke
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引用次数: 33

摘要

趋化是生物学中常见的一种重要的细胞反应。在许多趋化细胞中,调节运动的信号是由细胞表面结合特定趋化剂的G蛋白偶联受体启动的。这些受体与其他G蛋白偶联受体(包括视紫红质)具有重要的结构相似性,这是目前建模其结构的最佳起点。然而,趋化受体也有一些相对独特的结构特征,这些特征在其他gpcr中不太常见。趋化受体的趋化配体表现出各种各样的大小和化学性质,从小分子和多肽到蛋白质配体。因此,不同的趋化受体已经进化出专门的机制来进行配体结合和受体激活的早期步骤。跨膜信号传导的机制目前正在深入研究中,已经提出了几种跨膜螺旋不同构象重排的替代机制。一些趋化受体被提出形成二聚体,并且在某些情况下二聚体的形成被提出在跨膜信号传导中发挥作用。原则上,跨膜信号传导过程中发生的结构和动态变化可能是针对不同受体的,或者可能是广泛保守的。广泛的诱变研究已经开展,并已开始确定参与配体结合,受体激活和跨膜信号传导的关键残基。
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Chemotaxis receptors and signaling.

Chemotaxis is an important cellular response common in biology. In many chemotaxing cells the signal that regulates movement is initiated by G protein-coupled receptors on the cell surface that bind specific chemoattractants. These receptors share important structural similarities with other G protein-coupled receptors, including rhodopsin, which currently serves as the best starting point for modeling their structures. However, the chemotaxis receptors also share a number of relatively unique structural features that are less common in other GPCRs. The chemoattractant ligands of chemotaxis receptors exhibit a broad variety of sizes and chemical properties, ranging from small molecules and peptides to protein ligands. As a result, different chemotaxis receptors have evolved specialized mechanisms for the early steps of ligand binding and receptor activation. The mechanism of transmembrane signaling is currently under intensive study and several alternate mechanisms proposing different conformational rearrangements of the transmembrane helices have been proposed. Some chemotaxis receptors are proposed to form dimers, and in certain cases dimer formation is proposed to play a role in transmembrane signaling. In principle the structural and dynamical changes that occur during transmembrane signaling could be specialized for different receptors, or could be broadly conserved. Extensive mutagenesis studies have been carried out, and have begun to identify critical residues involved in ligand binding, receptor activation, and transmembrane signaling.

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