GPCRs globally coevolved with receptor activity-modifying proteins, RAMPs
GPCRs globally coevolved with receptor activity-modifying proteins, RAMPs
复制标题
DOI：
10.1073/pnas.1713074114
复制
发表时间：
2017-11-07
影响因子：
11.1
通讯作者：
Sakmar, Thomas P.
中科院分区：
文献类型：
--
作者：
Barbash, Shahar;Lorenzen, Emily;Sakmar, Thomas P.
受体活性修饰蛋白（RAMP）在人体组织中广泛表达，在某些情况下，已被证明会影响G蛋白偶联受体（GPCR）的表面表达或配体特异性。然而，RAMP-GPCR相互作用是否普遍存在，以及其功能后果的性质，在很大程度上仍然未知。在人类中，有三种RAMP和超过800种表达的GPCR，使得直接实验方法具有挑战性。我们分析了所有现有测序生物的相关基因组数据。我们发现RAMP和GPCR往往在同一物种中具有直系同源物，并且具有相同程度的相关系统发育树，或者高于在细胞信号传导中起关键作用的其他相互作用蛋白对。此外，得到的RAMP-GPCR相互作用图谱表明RAMP 1和RAMP 3与相同的GPCR组相互作用，这意味着功能冗余。我们接下来分析了人类转录组，发现了GPCR和RAMP的表达相关性。我们的研究结果表明，全球协同进化的GPCR和RAMPS和支持的假设，GPCR全球互动与RAMPs在细胞信号通路。
Receptor activity-modifying proteins (RAMPs) are widely expressed in human tissues and, in some cases, have been shown to affect surface expression or ligand specificity of G-protein-coupled receptors (GPCRs). However, whether RAMP-GPCR interactions are widespread, and the nature of their functional consequences, remains largely unknown. In humans, there are three RAMPs and over 800 expressed GPCRs, making direct experimental approaches challenging. We analyzed relevant genomic data from all currently available sequenced organisms. We discovered that RAMPs and GPCRs tend to have orthologs in the same species and have correlated phylogenetic trees to the same extent, or higher than other interacting protein pairs that play key roles in cellular signaling. In addition, the resulting RAMP-GPCR interaction map suggests that RAMP1 and RAMP3 interact with the same set of GPCRs, which implies functional redundancy. We next analyzed human transcriptomes and found expression correlation for GPCRs and RAMPs. Our results suggest global coevolution of GPCRs and RAMPS and support the hypothesis that GPCRs interact globally with RAMPs in cellular signaling pathways.