Structural insights into ligand recognition and activation of the succinate receptor SUCNR1 DOI Creative Commons
Aijun Liu,

Yezhou Liu,

Weijia Zhang

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(7), P. 114381 - 114381

Published: June 25, 2024

Succinate, a citric acid cycle intermediate, serves important functions in energy homeostasis and metabolic regulation. Extracellular succinate acts as stress signal through receptor (SUCNR1), class A G protein-coupled receptor. Research on signaling is hampered by the lack of high-resolution structures agonist-bound We present cryoelectron microscopy (cryo-EM) SUCNR1-Gi complexes bound to its non-metabolite derivative cis-epoxysuccinate. Key determinants for recognition cis conformation include R2817.39 Y832.64, while Y301.39 R993.29 participate binding both loop 2, F175ECL2 β-hairpin, forms hydrogen bond with caps pocket. At receptor-Gi interface, agonist induces rearrangement hydrophobic network transmembrane (TM)5 TM6, leading TM TM3 TM7. These findings extend our understanding SUCNR1, aiding development therapeutics

Language: Английский

Structural insights into ligand recognition and activation of the succinate receptor SUCNR1 DOI Creative Commons
Aijun Liu,

Yezhou Liu,

Weijia Zhang

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(7), P. 114381 - 114381

Published: June 25, 2024

Succinate, a citric acid cycle intermediate, serves important functions in energy homeostasis and metabolic regulation. Extracellular succinate acts as stress signal through receptor (SUCNR1), class A G protein-coupled receptor. Research on signaling is hampered by the lack of high-resolution structures agonist-bound We present cryoelectron microscopy (cryo-EM) SUCNR1-Gi complexes bound to its non-metabolite derivative cis-epoxysuccinate. Key determinants for recognition cis conformation include R2817.39 Y832.64, while Y301.39 R993.29 participate binding both loop 2, F175ECL2 β-hairpin, forms hydrogen bond with caps pocket. At receptor-Gi interface, agonist induces rearrangement hydrophobic network transmembrane (TM)5 TM6, leading TM TM3 TM7. These findings extend our understanding SUCNR1, aiding development therapeutics

Language: Английский

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