Cryo-EM structural elucidation and molecular mechanism of the GPR133-G13 signaling complex.

GPR133 is an adhesion-class G protein-coupled receptor (GPCR) that has recently been de-orphanized. Its functions are complex and multifaceted. While GPR133 is primarily recognized for coupling with the Gs subunit to mediate elevated intracellular cAMP levels, its potential engagement with alternative signaling pathways remains poorly characterized.

Progress in structure-based drug development targeting chemokine receptors.

As a critical subfamily of G protein-coupled receptors (GPCRs), chemokine receptors (CCRs) play pivotal regulatory roles in immune cell migration, inflammatory modulation, tissue regeneration, and tumor microenvironment (TME) remodeling. By specifically recognizing chemokine ligands, CCRs orchestrate immune cell trafficking and tissue positioning, with functional dysregulation implicated in infectious diseases, autoimmune disorders, neurodegenerative pathologies, and cancer. These receptors thus represent promising therapeutic targets.

Structural basis and biased signaling of proton sensation by GPCRs mediated by extracellular histidine rearrangement.

Proton sensing by G protein-coupled receptors (GPCRs) is crucial in many life activities. However, its underlying mechanism remains unclear. Here, we report 8 cryoelectron microscopy (cryo-EM) structures of human GPR4 and GPR68 at different pH values and in complex with Gs or Gq trimers or in apo state.

A force-sensitive adhesion GPCR is required for equilibrioception.

Equilibrioception (sensing of balance) is essential for mammals to perceive and navigate the three-dimensional world. A rapid mechanoelectrical transduction (MET) response in vestibular hair cells is crucial for detecting position and motion. Here, we identify the G protein-coupled receptor (GPCR) LPHN2/ADGRL2, expressed on the apical membrane of utricular hair cells, as essential for maintaining normal balance.

Identification, structure, and agonist design of an androgen membrane receptor.

Androgens, such as 5α-dihydrotestosterone (5α-DHT), regulate numerous functions by binding to nuclear androgen receptors (ARs) and potential unknown membrane receptors. Here, we report that the androgen 5α-DHT activates membrane receptor GPR133 in muscle cells, thereby increasing intracellular cyclic AMP (cAMP) levels and enhancing muscle strength. Further cryoelectron microscopy (cryo-EM) structural analysis of GPR133-Gs in complex with 5α-DHT or its derivative methenolone (MET) reveals the structural basis for androgen recognition.

Structures of the ADGRG2-G complex in apo and ligand-bound forms.

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.

Structures of the glucocorticoid-bound adhesion receptor GPR97-G complex.

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.

Hypotensive effects induced by herbal fomentation at Yongquan point.

Objective: This study aimed at assessing the adequacy of blood pressure (BP) control with the Chinese herbal fomentation at Yongquan point (K1).

Method: A total of 51 participants as a group were enrolled. In 10 participants as the subgroup, BP data were compared with those simultaneously recorded from the radial artery of the same side.

Chinese herbal fomentation at the Yongquan point (K1): a potential hypotensive regimen.

Objective: The goal of this research was to assess the adequacy of blood pressure (BP) control by applying Chinese herbal fomentation (a type of thermotherapy) at the Yongquan point (K1).

Methods: A total of 102 patients with hypertension, ages 39-55, were included in this study. After a baseline examination, each enrolled patient participated in one session per day lasting 24 hours for 3 continuous days, during which the Yongquan point (K1) on both sides of the body were fomented (given thermotherapy) with a mixture of Chinese herbs.