单跨膜 GPCR 调节蛋白:既不单一也不简单。

IF 13.6 1区 生物学 Q1 CELL BIOLOGY Protein & Cell Pub Date : 2024-05-28 DOI:10.1093/procel/pwad035
Meng Wang, Jianjun Lyu, Chao Zhang
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引用次数: 0

摘要

g蛋白偶联受体(GPCR)附属蛋白的发现从根本上重新定义了GPCR信号传导的药理学概念,证明了质膜上受体特异性和易受影响的下游细胞内级联反应的更复杂的分子基础。GPCR辅助蛋白不仅有助于受体的适当折叠和运输,而且还表现出选择性受体偏好。黑色素皮质素受体辅助蛋白(MRAP1和MRAP2)和受体活性修饰蛋白(RAMPs)是众所周知的两个单跨膜伙伴蛋白,分别调控黑色素皮质素受体(MC1R-MC5R)和胰高血糖素受体(GCGR)。特别是MRAP家族参与多种内分泌紊乱的病理控制,RAMPs参与葡萄糖稳态的内源性调节。然而,MRAP和RAMP蛋白在原子分辨率上调控受体信号的确切机制仍然未知。最近在Cell上发表的测定RAMP2结合GCGR复合物的进展(Krishna Kumar et al., 2023)揭示了RAMP2在促进细胞外受体动力学导致细胞质表面失活方面的重要性。此外,Cell Research (Luo et al., 2023)关于促肾上腺皮质激素(ACTH)结合的MC2R- gs -MRAP1复合物的新发现揭示了MRAP1在MC2R激活和配体识别特异性中的重要作用。在本文中,我们回顾了近十年来MRAP蛋白的一系列重要发现,以及最近MRAP- mc2r和RAMP-GCGR功能复合物的结构研究以及MRAP蛋白新的GPCR伴侣的扩展鉴定。深入了解单个跨膜辅助蛋白对GPCR的调控,将为开发治疗多种GPCR相关人类疾病的治疗药物提供有价值的见解。
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Single transmembrane GPCR modulating proteins: neither single nor simple.
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来源期刊
Protein & Cell
Protein & Cell CELL BIOLOGY-
CiteScore
24.00
自引率
0.90%
发文量
1029
审稿时长
6-12 weeks
期刊介绍: Protein & Cell is a monthly, peer-reviewed, open-access journal focusing on multidisciplinary aspects of biology and biomedicine, with a primary emphasis on protein and cell research. It publishes original research articles, reviews, and commentaries across various fields including biochemistry, biophysics, cell biology, genetics, immunology, microbiology, molecular biology, neuroscience, oncology, protein science, structural biology, and translational medicine. The journal also features content on research policies, funding trends in China, and serves as a platform for academic exchange among life science researchers.
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