The Biophysical Society of Japan (BSJ) ? Miyazaki Meeting, September 2019 Session 1SHP?frontier of structure-function studies to unveil diverse GPCR signaling
The Biophysical Society of Japan (BSJ) ? Miyazaki Meeting, September 2019 Session 1SHP?frontier of structure-function studies to unveil diverse GPCR signaling
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日本生物物理学会（BSJ）？
DOI：
10.1007/s12551-020-00689-2
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发表时间：
2020
影响因子：
--
通讯作者：
Suno Ryoji
中科院分区：
文献类型：
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作者：
Katayama Kota;Suno Ryoji
GPCR （G蛋白偶联受体）信号传导利用细胞外面对配体结合口袋和受体的细胞质结构域之间的变构偶联，选择性地与信号传感器相互作用。这种变构效应使受体的一个部位能够调节另一个空间上不同区域的功能。因此，了解配体诱导的受体构象变化和特异性换能器识别背后的分子机制对于开发基于gpcr的药物非常重要。本次研讨会旨在探讨GPCR信号转导的分子基础，探讨其结构功能研究的最新进展。六位演讲者使用他们的专业方法介绍了最新的GPCR研究（图1）。Ikuo Masuho开发了一种单平台分析方法，用于分析GPCR在几乎完整的G蛋白底物上的活性。（Masuho et al. 2018） Masataka Yanagawa通过观察活细胞中的单个受体分子分析了gpcr的动态行为。他和他的团队开发了一种单分子成像分析方法，用于评估配体对gpcr的影响。（Yanagawa et al. 2018） Hideaki Kato通过低温电子显微镜（cro - em）单粒子分析确定了人类神经紧张素受体1 (NTSR1)-G蛋白复合物的结构（图1）（Kato et al. 2019）。Hiroshi Kofuku用核磁共振测量了gpcr的动力学。为了了解磷酸化gpcr -抑制蛋白复合物形成的机制，他们对纳米圆盘脂质双层中磷酸化的β2-肾上腺素受体（β2AR）和磷酸化的β2AR-β-抑制蛋白1复合物进行了核磁共振分析。（Kofuku et al. 2018） Satoshi Yasuda在理论预测的基础上提出了对gpcr中热稳定突变的研究。他和他的团队开发了一种热稳定突变的理论预测方法，使用它们的自由能函数，该函数的重点是脂质双分子层内非极性链的平移熵作为熵项，蛋白质分子内氢键作为能项。（Yasuda et al. 2017）
GPCR (G protein-coupled receptor) signaling utilizes an allosteric coupling between the extracellular facing ligand-binding pocket and the cytoplasmic domain of the receptor selectively interacting with a signal transducer. This allosteric effect enables one site of the receptor to regulate the function of another spatially distinct region. Therefore, it is important to understand the molecular mechanisms behind ligand-induced changes in receptor conformation and specific transducer-recognition for the development of GPCR-based drugs. This symposium is dedicated to discussing the latest trends on the structurefunction studies to explore the molecular basis of GPCR signal transduction. Six presenters presented the latest GPCR research using their specialized methods (Fig. 1). Ikuo Masuho developed a single-platform assay for profiling GPCR activity on a nearly complete set of G protein substrates.(Masuho et al. 2018) Masataka Yanagawa analyzed the dynamic behavior of GPCRs by observing single receptor molecules in a living cell. He and his group have developed a single-molecule imaging analysis for assessing the effects of ligands on GPCRs.(Yanagawa et al. 2018) Hideaki Kato determined the structure of the human neurotensin receptor 1 (NTSR1)-G protein complex by cryoelectron microscopy (cryo-EM) single-particle analysis (Fig. 1).(Kato et al. 2019).Hiroshi Kofuku measured the dynamics of GPCRs using NMR. To understand the mechanism underlying the formation of the phosphorylated GPCR-arrestin complex, they performed NMR analyses of the phosphorylated β2-adrenoceptor (β2AR) and the phosphorylated β2AR-β-arrestin 1 complex in the lipid bilayers of nanodisc.(Kofuku et al. 2018) Satoshi Yasuda presented the search for thermostabilizing mutations in GPCRs on the basis of theoretical prediction. He and his group developed a theoretical prediction method for thermostabilizing mutations using their free-energy function which is focused on the translational entropy of nonpolar chains within the lipid bilayer as the entropic term and the protein intramolecular hydrogen bonding as the energetic term.(Yasuda et al. 2017)