Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.
Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.
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DOI：
10.1124/pharmrev.120.000180
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发表时间：
2023-01
影响因子：
21.1
通讯作者：
中科院分区：
文献类型：
--
作者：
已知G蛋白偶联受体（gpcr）与其他几种类型的整体膜蛋白相互作用，调节其生物学和药理学。然而，这些相互作用的程度及其作用机制尚不清楚。例如，一类与gpcr相互作用的蛋白，受体活性修饰蛋白（RAMPs），由三种相关且普遍表达的单跨膜跨蛋白组成。RAMP家族在二十多年前被发现，从那时起，GPCR-RAMP相互作用及其对受体运输和配体选择性的功能影响已被记录为几种分泌素（B类）gpcr，最著名的是降钙素受体样受体。最近的生物信息学和多路实验研究表明，GPCR-RAMP相互作用可能比以前预期的要广泛得多。最近，低温电子显微镜已经提供了GPCR-RAMP配体复合物的高分辨率结构，并且已经开发出靶向GPCR-RAMP复合物的药物。在这篇综述中，我们总结了发现GPCR-RAMP相互作用及其功能后果的最新技术进展，并强调了未来进展的前景。我们还根据对当前文献的回顾，提供了最新的GPCR-RAMP相互作用的报告列表。受体活性修饰蛋白（RAMPs）已成为G蛋白偶联受体（GPCR）生物学和药理学许多方面的调节剂。应用新方法研究膜蛋白-蛋白相互作用表明，RAMPs与比以前已知的更多的gpcr相互作用。这些发现，特别是与膜蛋白复合物的结构研究相结合，对推进GPCR靶向药物的发现以及对GPCR药理学、生物学和调控的理解具有重要意义。
G protein-coupled receptors (GPCRs) are known to interact with several other classes of integral membrane proteins that modulate their biology and pharmacology. However, the extent of these interactions and the mechanisms of their effects are not well understood. For example, one class of GPCR-interacting proteins, receptor activity-modifying proteins (RAMPs), comprise three related and ubiquitously expressed single-transmembrane span proteins. The RAMP family was discovered more than two decades ago, and since then GPCR–RAMP interactions and their functional consequences on receptor trafficking and ligand selectivity have been documented for several secretin (class B) GPCRs, most notably the calcitonin receptor-like receptor. Recent bioinformatics and multiplexed experimental studies suggest that GPCR–RAMP interactions might be much more widespread than previously anticipated. Recently, cryo-electron microscopy has provided high-resolution structures of GPCR–RAMP–ligand complexes, and drugs have been developed that target GPCR–RAMP complexes. In this review, we provide a summary of recent advances in techniques that allow the discovery of GPCR–RAMP interactions and their functional consequences and highlight prospects for future advances. We also provide an up-to-date list of reported GPCR–RAMP interactions based on a review of the current literature. Receptor activity-modifying proteins (RAMPs) have emerged as modulators of many aspects of G protein-coupled receptor (GPCR)biology and pharmacology. The application of new methodologies to study membrane protein–protein interactions suggests that RAMPs interact with many more GPCRs than had been previously known. These findings, especially when combined with structural studies of membrane protein complexes, have significant implications for advancing GPCR-targeted drug discovery and the understanding of GPCR pharmacology, biology, and regulation.
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影响因子：
5
作者：
Barrick CJ;Lenhart PM;Dackor RT;Nagle E;Caron KM
通讯作者：
Caron KM
影响因子：
4.8
作者：
Bomberger, JM;Spielman, WS;Parameswaran, N
通讯作者：
Parameswaran, N
DOI：
10.1093/protein/7.2.195
发表时间：
1994-02-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
ATTWOOD, TK;FINDLAY, JBC
通讯作者：
FINDLAY, JBC
DOI：
10.1073/pnas.1713074114
发表时间：
2017-11-07
影响因子：
11.1
作者：
Barbash, Shahar;Lorenzen, Emily;Sakmar, Thomas P.
通讯作者：
Sakmar, Thomas P.
DOI：
10.1126/science.1262110
发表时间：
2015-05-08
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
GTEx Consortium
通讯作者：
GTEx Consortium