Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors.
Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors.
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DOI：
10.3389/fphar.2015.00264
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发表时间：
2015
影响因子：
5.6
通讯作者：
Yan EC
中科院分区：
文献类型：
--
作者：
Culhane KJ;Liu Y;Cai Y;Yan EC
B G蛋白偶联受体（GPCRs）家族虽然只有15个成员，但在激素跨膜信号转导中起着重要作用。家族B GPCR是用于开发从代谢紊乱到神经紊乱的疾病的治疗剂的药物靶标。尽管它们很重要，但由于功能受体的表达和纯化对于生物物理表征的量的挑战，家族B GPCR的活化的分子机制在很大程度上仍未被探索。目前，没有全长家族B GPCR的晶体结构可用。然而，关键结构域的结构，包括细胞外配体结合区和七螺旋跨膜区，已经解决了X射线晶体学和NMR，提供了深入了解配体识别和选择性的机制，和细胞膜内的螺旋排列。此外，生物物理和生物化学方法已被用于探索功能，信号传导的关键残基，以及信号传导过程的动力学和动力学。本文综述了B家族GPCRs在分子水平上的信号转导机制，并对B家族GPCRs机制研究面临的挑战和前景进行了展望。
Although family B G protein-coupled receptors (GPCRs) contain only 15 members, they play key roles in transmembrane signal transduction of hormones. Family B GPCRs are drug targets for developing therapeutics for diseases ranging from metabolic to neurological disorders. Despite their importance, the molecular mechanism of activation of family B GPCRs remains largely unexplored due to the challenges in expression and purification of functional receptors to the quantity for biophysical characterization. Currently, there is no crystal structure available of a full-length family B GPCR. However, structures of key domains, including the extracellular ligand binding regions and seven-helical transmembrane regions, have been solved by X-ray crystallography and NMR, providing insights into the mechanisms of ligand recognition and selectivity, and helical arrangements within the cell membrane. Moreover, biophysical and biochemical methods have been used to explore functions, key residues for signaling, and the kinetics and dynamics of signaling processes. This review summarizes the current knowledge of the signal transduction mechanism of family B GPCRs at the molecular level and comments on the challenges and outlook for mechanistic studies of family B GPCRs.