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G蛋白偶联受体(GPCRs)是与G蛋白相偶联的七次跨膜受体,其成员有上千种,是重要的药物靶点之一。目前,GPCRs相关药物占市场上药物的40%-50%。在过去的十年中,对GPCRs主要以单体的形式存在着的这一假说做出了重新评估,大量事实证明GPCRs也能以同源或异源二聚体,甚至是高阶寡聚体的形式存在,比较热门的领域是GPCRs二聚化。最近研究表明同源或异源二聚化有不同于单体的特异功能特征,包括配体识别、信号转导、运输等。同时,在较少副作用治疗疾病的新药开发上,具有不同病理和信号转导途径的二聚体的出现开辟了新的领域。本综述主要介绍二聚体的特异结构及其特异的信号转导途径,从而有助于在GPCRs药物开发中取得丰硕的成果。
G protein-coupled receptors (GPCRs) are seven-pass transmembrane receptors coupled to the G protein, with thousands of members, and are one of the important drug targets. At present, GPCRs-related drugs account for 40% -50% of the drugs on the market. Over the past decade, the hypothesis that GPCRs predominate in the form of monomers has been re-evaluated, and a large body of evidence has shown that GPCRs can also target homodimers or heterodimers, or even higher-order oligomers The form of the existence of the more popular area is GPCRs dimerization. Recent studies show that homologous or heterodimerization has specific functional characteristics that are different from monomers, including ligand recognition, signal transduction, transport and the like. At the same time, the advent of dimers with different pathologies and signal transduction pathways opens up new avenues for the development of new drugs with fewer side effects to treat the disease. This review will focus on the specific structure of dimers and their specific signal transduction pathways, which will help to achieve fruitful results in the development of GPCRs drugs.