9bi6 | pdb_00009bi6

Human proton sensing receptor GPR68 in complex with miniGsq

spinqualitylabelsall models 9bi6, resolution 2.90Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9bi6 is a 5 chain structure with sequence from Homo sapiens, Lama glama and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.9Å Ligands: Y01 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function GBB1_HUMAN Guanine nucleotide-binding proteins (G proteins) are involved as a modulator or transducer in various transmembrane signaling systems. The beta and gamma chains are required for the GTPase activity, for replacement of GDP by GTP, and for G protein-effector interaction. Publication Abstract from PubMed Three proton-sensing G protein-coupled receptors (GPCRs)-GPR4, GPR65, and GPR68-respond to extracellular pH to regulate diverse physiology. How protons activate these receptors is poorly understood. We determined cryogenic-electron microscopy (cryo-EM) structures of each receptor to understand the spatial arrangement of proton-sensing residues. Using deep mutational scanning (DMS), we determined the functional importance of every residue in GPR68 activation by generating approximately 9,500 mutants and measuring their effects on signaling and surface expression. Constant-pH molecular dynamics simulations provided insights into the conformational landscape and protonation patterns of key residues. This unbiased approach revealed that, unlike other proton-sensitive channels and receptors, no single site is critical for proton recognition. Instead, a network of titratable residues extends from the extracellular surface to the transmembrane region, converging on canonical motifs to activate proton-sensing GPCRs. Our approach integrating structure, simulations, and unbiased functional interrogation provides a framework for understanding GPCR signaling complexity. Molecular basis of proton sensing by G protein-coupled receptors.,Howard MK, Hoppe N, Huang XP, Mitrovic D, Billesbolle CB, Macdonald CB, Mehrotra E, Rockefeller Grimes P, Trinidad DD, Delemotte L, English JG, Coyote-Maestas W, Manglik A Cell. 2024 Dec 26:S0092-8674(24)01373-4. doi: 10.1016/j.cell.2024.11.036. PMID:39753132 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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