G蛋白偶联受体的探索之路—记2012年诺贝尔化学奖得主Robert J.Lefkowitz和Brian K.Kobilka

The Discovery Road of G-protein-coupled Receptors:Introduction of the Nobel Prize Winners in Chemistry 2012,Robert J.Lefkowitz and Brian K.Kobilka

2012年诺贝尔化学奖颁给了Robert J.Lefkowitz和Brian K.Kobilka,基于他们在G蛋白偶联受体(G-protein-coupled receptors,GPCRs)研究领域的杰出贡献.Robert J.Lefkowitz是现代GPCRs研究的奠基人.他开创了利用放射配体研究受体功能的先河,证实了受体的存在,率先得到受体克隆,发现了G蛋白偶联受体激酶与β-arrestins介导受体的减敏与内吞,并发现了β-arrestins的信号转导功能.Brian K.Kobilka多年来坚持不懈,开创了很多GPCRs晶体学上的突破性方法,是揭示β2肾上腺素受体晶体结构的第一人,引导了近年来GPCRs受体晶体结构领域的迅猛发展.尤其令人惊叹的是,他展示了β2肾上腺素受体激活瞬间的晶体构象.本文综述了两位杰出科学家探索GPCRs的科研经历及成果,希望读者能够有所借鉴.

The Nobel Prize in Chemistry 2012 was awarded jointly to Robert J. Lefkowitz and Brian K. Kobilka based on their remarkable contributions to the studies of G-protein-coupled receptors （GPCRs）. Robert J. Lefkowitz is the Godfather of the modern GPCRs studies. He developed the radioligand binding assay to study the receptors, verified the existence of the receptors, cloned the first GPCR gene, found G protein-coupled receptor kinases （GRKs） and β-arrestins which mediate the desensitization and endocytosis of the receptors, and found the siganling pathways mediated by β-arrestins. Brian K. Kobilka developed several breakthrough methods in GPCRs crystallography. His team first solved the high-resolution structure of β2-adrenergic receptor. His findings led rapid development of GPCRs crystallography. Amazingly, he and his research team got a snapshot of the β-adrenergic receptor at the exact moment when it is activated. The present review summarizes the GPCRs discovery experiences of these two outstanding scientists.