8iei
Cryo-EM structure of GPR156A/B of G-protein free GPR156 (local refine)
Structural highlights
DiseaseGP156_HUMAN The disease is caused by variants affecting the gene represented in this entry. FunctionGP156_HUMAN Orphan G-protein coupled receptor involved in the regulation of hair cell orientation in mechanosensory organs of the inner ear. It is required to trigger a 180 degree reversal in hair cell orientation, creating a virtual line of polarity reversal (LPR) across which stereociliary bundles are arranged in opposite orientations.[UniProtKB:Q6PCP7] Publication Abstract from PubMedClass C G-protein-coupled receptors (GPCRs) are activated through binding of agonists to the large extracellular domain (ECD) followed by rearrangement of the transmembrane domains (TMDs). GPR156, a class C orphan GPCR, is unique because it lacks an ECD and exhibits constitutive activity. Impaired GPR156-G(i) signaling contributes to loss of hearing. Here we present the cryo-electron microscopy structures of human GPR156 in the G(o)-free and G(o)-coupled states. We found that an endogenous phospholipid molecule is located within each TMD of the GPR156 dimer. Asymmetric binding of Galpha to the phospholipid-bound GPR156 dimer restructures the first and second intracellular loops and the carboxy-terminal part of the elongated transmembrane 7 (TM7) without altering dimer conformation. Our findings reveal that GPR156 is a transducer for phospholipid signaling. Constant binding of abundant phospholipid molecules and the G-protein-induced reshaping of the cytoplasmic face provide a basis for the constitutive activation of GPR156. Constitutive activation mechanism of a class C GPCR.,Shin J, Park J, Jeong J, Lam JH, Qiu X, Wu D, Kim K, Lee JY, Robinson CV, Hyun J, Katritch V, Kim KP, Cho Y Nat Struct Mol Biol. 2024 Apr;31(4):678-687. doi: 10.1038/s41594-024-01224-7. , Epub 2024 Feb 8. PMID:38332368[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
