小柯机器人

近日，美国斯坦福大学医学院Georgios Skiniotis及其研究小组解析出代谢型GABA_B受体的结构。该研究于2020年6月24日在线发表于国际学术期刊《自然》。

Title: Structures of metabotropic GABA B receptor

Author: Makaa M. Papasergi-Scott, Michael J. Robertson, Alpay B. Seven, Ouliana Panova, Jesper M. Mathiesen, Georgios Skiniotis

Issue&Volume: 2020-06-24

Abstract: GABA (γ-aminobutyric acid) stimulation of the metabotropic GABAB receptor results in prolonged inhibition of neurotransmission that is central to brain physiology1. GABAB belongs to the Family C of G protein-coupled receptors (GPCRs), which operate as dimers to relay synaptic neurotransmitter signals into a cellular response through the binding and activation of heterotrimeric G proteins2,3. GABAB, however, is unique in its function as an obligate heterodimer in which agonist binding and G protein activation take place on distinct subunits4,5. Here we show structures of heterodimeric and homodimeric full-length GABAB receptors. Complemented by cellular signaling assays and atomistic simulations, the structures reveal an essential role for the GABAB extracellular loop 2 (ECL2) in relaying structural transitions by ordering the linker connecting the extracellular ligand-binding domain to the transmembrane region. Furthermore, the ECL2 of both GABAB subunits caps and interacts with the hydrophilic head of a phospholipid occupying the extracellular half of the transmembrane domain, thereby providing a potentially crucial link between ligand binding and the receptor core that engages G protein. These results provide a starting framework to decipher mechanistic modes of signal transduction mediated by GABAB dimers and have important implications for rational drug design targeting these receptors.

DOI: 10.1038/s41586-020-2469-4

Source: https://www.nature.com/articles/s41586-020-2469-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
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