A5030239084- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Adipose Tissue and Metabolism
- Sphingolipid Metabolism and Signaling
- Cancer, Stress, Anesthesia, and Immune Response
- Nitric Oxide and Endothelin Effects
- Neuroscience and Neuropharmacology Research
- Wireless Networks and Protocols
- Tryptophan and brain disorders
- Inflammasome and immune disorders
- Cellular transport and secretion
- Mass Spectrometry Techniques and Applications
- Cooperative Communication and Network Coding
- Privacy-Preserving Technologies in Data
- Ion Transport and Channel Regulation
- Ion channel regulation and function
Chinese University of Hong Kong
2025
Chinese University of Hong Kong, Shenzhen
2022-2024
GPR17 is a class A orphan G protein-coupled receptor (GPCR) expressed in neurons and oligodendrocyte progenitors of the central nervous system (CNS). The signalling occurs through heterotrimeric Gi, but its activation mechanism unclear. Here, we employed cryo-electron microscopy (cryo-EM) technology to elucidate structure activated GPR17-Gi complex. 3.02 Å resolution structure, together with mutagenesis studies, revealed that extracellular loop2 occupied orthosteric binding pocket promote...
<title>Abstract</title> Yohimbine, a potent alpha2A-adrenergic receptor (α2AAR) antagonist, was found to carry therapeutic potential for type 2 diabetes through improving insulin release. However, adverse side effects mediated by its actions in the brain hampered use. Here, we have developed novel peripherally acting α2AAR CDS479-2, based on molecular docking analysis and modification of yohimbine's structure. The inactive-state structures α2AAR, either bound yohimbine, or were elucidated...
To accomplish concerted physiological reactions, nature has diversified functions of a single hormone at least two primary levels: 1) Different receptors recognize the same hormone, and 2) different cellular effectors couple to hormone–receptor pair [R.P. Xiao, Sci STKE 2001 , re15 (2001); L. Hein, J. D. Altman, B.K. Kobilka, Nature 402 181–184 (1999); Y. Daaka, M. Luttrell, R. Lefkowitz, 390 88–91 (1997)]. Not only these questions lie in heart actions receptor signaling but also dissecting...
Yohimbine, a potent alpha2A-adrenergic receptor (α2AAR) antagonist, was found therapeutic potential for type 2 diabetes through improving insulin release. However, the adverse side effects mediated by its actions in brain hampered use. Here, based on molecular docking analysis and structural modification, we have developed novel peripherally acting yohimbine derivative (CDS479-2). CryoEM data that CDS479-2 similar interactions with structure of α2AAR. Importantly, shows α2AAR antagonist...
Abstract S1PR4 is one of five subtypes sphingosine 1-phosphate receptors (S1PRs) that regulate immune cell functioning, with functional distinctions to other subtypes. S1PR1-targeted modulators caused serious cardiac and vascular adverse effects because S1PR1 was expressed throughout the whole body. Since only in lung lymphoid cells, S1PR4-targeted might not trigger these side effects. However, development S1PR4-specific agonists greatly hindered lack activated structure. Here, we resolved...