Molecular switches in GPCRs
Molecular switches in GPCRs
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DOI：
10.1016/j.sbi.2019.03.017
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发表时间：
2019-04-01
影响因子：
6.8
通讯作者：
Filipek, Slawomir
中科院分区：
文献类型：
--
作者：
Filipek, Slawomir
GPCR中的分子开关能够将信号从通常位于细胞外表面附近的激动剂结合位点传递到受体的细胞内部分。开关通常与跨膜螺旋（TM）上的保守结构基序相关联，并且它们伴随着向拨动开关中的中心残基提供信号的相邻残基。在锁是分子开关的情况下，它们在激动剂结合时断裂（永久或暂时）。开关的级联作用与水分子的流入相关，以形成连接受体两侧的通路。这些开关消除了疏水屏障，促进了水的移动，而水分子有助于重新排列受体内部的氢键网络。
Molecular switches in GPCRs enable passing the signal from the agonist binding site, usually located close to the extracellular surface, to the intracellular part of the receptor. The switches are usually associated with conserved structural motifs on transmembrane helices (TMs), and they are accompanied by adjacent residues which provide the signal to the central residue in the toggle switch. In case of locks being the molecular switches, they are breaking (permanently or temporarily) upon agonist binding. Cascade action of switches is correlated with influx of water molecules to form a pathway linking both sides of the receptor. The switches remove the hydrophobic barriers and facilitate water movement while water molecules help to rearrange the hydrogen bond network inside the receptor.