分类: 药物科学 >> 结构生物学 提交时间: 2024-02-24
摘要: The orphan receptor GPR30, previously classified as a G protein-coupled estrogen receptor (GPER), has been a subject of debate regarding its ligand specificity. Through an integrative approach combining structure elucidation, biochemical binding, and cell signaling assays, we demonstrate that estrogen does not directly bind to or activate GPR30. Cryo-EM structures of GPR30 reveal an unexpected hydrophilic ligand-binding pocket, with striking differences from classical hydrophobic steroid-binding sites, inconsistent with estrogen binding. We further confirmed hydrophilic agonists like Lys05 as true activators of GPR30, providing structural insights into their binding mechanism and receptor activation. Our findings necessitate a paradigm shift in defining GPR30’s role in estrogen signaling, indicating that its activation occurs through mechanisms independent of estrogen binding. This study opens new avenues for developing targeted GPR30 ligands and reinterpreting its role in estrogen-mediated processes.
分类: 天文学 >> 天文仪器与技术 提交时间: 2024-02-07 合作期刊: 《天文技术与仪器(英文)》
摘要:The Jiao Tong University Spectroscopic Telescope (JUST) is a 4.4-meter f/6.0 segmented-mirror telescope dedicated to spectroscopic observations. The JUST primary mirror is composed of 18 hexagonal segments, each with a diameter of 1.1 m. JUST provides two Nasmyth platforms for placing science instruments. One Nasmyth focus fits a field of view of 10 ′ and the other has an extended field of view of 1.2° with correction optics. A tertiary mirror is used to switch between the two Nasmyth foci. JUST will be installed at a site at Lenghu in Qinghai Province, China, and will conduct spectroscopic observations with three types of instruments to explore the dark universe, trace the dynamic universe, and search for exoplanets: (1) a multi-fiber (2000 fibers) medium-resolution spectrometer (R=4 000−5 000) to spectroscopically map galaxies and large-scale structure; (2) an integral field unit (IFU) array of 500 optical fibers and/or a long-slit spectrograph dedicated to fast follow-ups of transient sources for multi-messenger astronomy; (3) a high-resolution spectrometer (R~100 000) designed to identify Jupiter analogs and Earth-like planets, with the capability to characterize the atmospheres of hot exoplanets.