Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.

IF 19.3 1区 医学 Q1 PHARMACOLOGY & PHARMACY Pharmacological Reviews Pub Date : 2023-01-01 Epub Date: 2022-12-08 DOI:10.1124/pharmrev.120.000180
Ilana B Kotliar, Emily Lorenzen, Jochen M Schwenk, Debbie L Hay, Thomas P Sakmar
{"title":"Elucidating the Interactome of G Protein-Coupled Receptors and Receptor Activity-Modifying Proteins.","authors":"Ilana B Kotliar, Emily Lorenzen, Jochen M Schwenk, Debbie L Hay, Thomas P Sakmar","doi":"10.1124/pharmrev.120.000180","DOIUrl":null,"url":null,"abstract":"<p><p>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. SIGNIFICANCE STATEMENT: 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.</p>","PeriodicalId":19780,"journal":{"name":"Pharmacological Reviews","volume":null,"pages":null},"PeriodicalIF":19.3000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ef/a7/pharmrev.120.000180.PMC9832379.pdf","citationCount":"9","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacological Reviews","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1124/pharmrev.120.000180","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/12/8 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 9

Abstract

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. SIGNIFICANCE STATEMENT: 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.

Abstract Image

Abstract Image

Abstract Image

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
G蛋白偶联受体与受体活性修饰蛋白相互作用的研究。
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。意义声明: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。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
Pharmacological Reviews
Pharmacological Reviews 医学-药学
CiteScore
34.70
自引率
0.50%
发文量
40
期刊介绍: Pharmacological Reviews is a highly popular and well-received journal that has a long and rich history of success. It was first published in 1949 and is currently published bimonthly online by the American Society for Pharmacology and Experimental Therapeutics. The journal is indexed or abstracted by various databases, including Biological Abstracts, BIOSIS Previews Database, Biosciences Information Service, Current Contents/Life Sciences, EMBASE/Excerpta Medica, Index Medicus, Index to Scientific Reviews, Medical Documentation Service, Reference Update, Research Alerts, Science Citation Index, and SciSearch. Pharmacological Reviews offers comprehensive reviews of new pharmacological fields and is able to stay up-to-date with published content. Overall, it is highly regarded by scholars.
期刊最新文献
Ironing Out the Mechanism of gp130 Signaling The 75-Year Anniversary of the Department of Physiology and Pharmacology at Karolinska Institutet—Examples of Recent Accomplishments and Future Perspectives Glatiramer Acetate for the Treatment of Multiple Sclerosis: From First-Generation Therapy to Elucidation of Immunomodulation and Repair How to drug a cloud? Targeting intrinsically disordered proteins. Pharmacological therapies for male infertility.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1