分类: 药物科学 >> 结构生物学 提交时间: 2024-02-29
摘要: Succinic acid, a tricarboxylic acid (TCA) cycle intermediate, significantly influences mitochondrial reactive oxygen species homeostasis through the G protein-coupled succinate receptor (SUCR1, also called GPR91), linking it to various physiological and pathological processes. Despite SUCR1’s pivotal role in mediating effects leading to liver fibrosis, hypertension, angiogenesis, inflammation, and offering a therapeutic target for multiple diseases, its activation mechanism by diverse ligands and interaction with downwards G protein remains poorly understood. This study presents the cryo-electron microscopy (cryo-EM) structures of SUCR1 in complex with inhibitory G protein (Gi) bound to succinic acid, maleic acid, and compound 31, a high-affinity agonist. These structures elucidate the distinct ligand binding modes, uncover the activation signal cascade, and detail the G protein coupling mechanism of SUCR1. Our findings provide a comprehensive structural basis for SUCR1 activation, paving the way for structure-based drug design aimed at SUCR1-related pathologies.
分类: 光学 >> 量子光学 提交时间: 2023-02-19
摘要: We present a nonlinear multimode superconducting electroacoustic system, where the interplay between superconducting kinetic inductance and piezoelectric strong coupling establishes an effective Kerr nonlinearity among multiple acoustic modes at 10 GHz that could hardly be achieved via intrinsic mechanical nonlinearity. By exciting this multimode Kerr system with a single microwave tone, we further demonstrate a coherent electroacoustic frequency comb and provide theoretical understanding of multimode nonlinear interaction in the superstrong coupling limit. This nonlinear superconducting electroacoustic system sheds light on the active control of multimode resonator systems and offers an enabling platform for the dynamic study of microcombs at microwave frequencies.