Identification of a carbohydrate recognition motif of purinergic receptors.

ABSTRACT: As a major class of biomolecules, carbohydrates play indispensable roles in various biological processes. However, it remains largely unknown how carbohydrates directly modulate important drug targets, such as G-protein coupled receptors (GPCRs). Here, we employed P2Y purinoceptor 14 (P2Y14), a drug target for inflammation and immune responses, to uncover the sugar nucleotide activation of GPCRs. Integrating molecular dynamics simulation with functional study, we identified the uridine diphosphate (UDP)-sugar-binding site on P2Y14, and revealed that a UDP-glucose might activate the receptor by bridging the transmembrane (TM) helices 2 and 7. Between TM2 and TM7 of P2Y14, a conserved salt bridging chain (K^2.60-D^2.64-K^7.35-E^7.36 [KDKE]) was identif

SUBMITTER: Zhao L 

PROVIDER: S-EPMC10642967 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature