Publications by authors named "Yuqi Ping"
Adhesion G protein-coupled receptors are elusive in terms of their structural information and ligands. Here, we solved the cryogenic-electron microscopy (cryo-EM) structure of apo-ADGRG2, an essential membrane receptor for maintaining male fertility, in complex with a G trimer. Whereas the formations of two kinks were determinants of the active state, identification of a potential ligand-binding pocket in ADGRG2 facilitated the screening and identification of dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate and deoxycorticosterone as potential ligands of ADGRG2.
View Article and Find Full Text PDFArticle Synopsis
- Adhesion G-protein-coupled receptors (aGPCRs) play vital roles in various biological processes, and their activation often involves a specific internal sequence called the Stachel sequence which assumes a unique structural formation in their binding sites.
- Researchers used cryogenic electron microscopy to study two aGPCRs, GPR133 and GPR114, revealing that the Stachel sequences interact with specific motifs in their transmembrane domains, critical for receptor activation.
- The study identifies key mechanisms in how these receptors are activated and couple with G proteins, particularly highlighting a common binding interface and unique structural features of GPR114 that facilitate its interactions.
Adhesion G-protein-coupled receptors (GPCRs) are a major family of GPCRs, but limited knowledge of their ligand regulation or structure is available. Here we report that glucocorticoid stress hormones activate adhesion G-protein-coupled receptor G3 (ADGRG3; also known as GPR97), a prototypical adhesion GPCR. The cryo-electron microscopy structures of GPR97-G complexes bound to the anti-inflammatory drug beclomethasone or the steroid hormone cortisol revealed that glucocorticoids bind to a pocket within the transmembrane domain.
View Article and Find Full Text PDFThe G-protein-coupled bile acid receptor (GPBAR) conveys the cross-membrane signalling of a vast variety of bile acids and is a signalling hub in the liver-bile acid-microbiota-metabolism axis. Here we report the cryo-electron microscopy structures of GPBAR-G complexes stabilized by either the high-affinity P395 or the semisynthesized bile acid derivative INT-777 at 3 Å resolution. These structures revealed a large oval pocket that contains several polar groups positioned to accommodate the amphipathic cholic core of bile acids, a fingerprint of key residues to recognize diverse bile acids in the orthosteric site, a putative second bile acid-binding site with allosteric properties and structural features that contribute to bias properties.
View Article and Find Full Text PDF