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8ZH8

Human GPR103 -Gq complex bound to QRFP26

Summary for 8ZH8
Entry DOI10.2210/pdb8zh8/pdb
EMDB information60096
DescriptorPyroglutamylated RF-amide peptide receptor, nanobody Nb35, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, ... (7 entities in total)
Functional Keywordsgpcr, membrane protein, membrane protein-immune system complex, membrane protein/immune system
Biological sourceHomo sapiens (human)
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Total number of polymer chains7
Total formula weight174089.31
Authors
Iwama, A.,Akasaka, H.,Sano, F.K.,Oshima, H.S.,Shihoya, W.,Nureki, O. (deposition date: 2024-05-10, release date: 2024-07-03, Last modification date: 2024-11-06)
Primary citationIwama, A.,Kise, R.,Akasaka, H.,Sano, F.K.,Oshima, H.S.,Inoue, A.,Shihoya, W.,Nureki, O.
Structure and dynamics of the pyroglutamylated RF-amide peptide QRFP receptor GPR103.
Nat Commun, 15:4769-4769, 2024
Cited by
PubMed Abstract: Pyroglutamylated RF-amide peptide (QRFP) is a peptide hormone with a C-terminal RF-amide motif. QRFP selectively activates a class A G-protein-coupled receptor (GPCR) GPR103 to exert various physiological functions such as energy metabolism and appetite regulation. Here, we report the cryo-electron microscopy structure of the QRFP26-GPR103-G complex at 3.19 Å resolution. QRFP26 adopts an extended structure bearing no secondary structure, with its N-terminal and C-terminal sides recognized by extracellular and transmembrane domains of GPR103 respectively. This movement, reminiscent of class B1 GPCRs except for orientation and structure of the ligand, is critical for the high-affinity binding and receptor specificity of QRFP26. Mutagenesis experiments validate the functional importance of the binding mode of QRFP26 by GPR103. Structural comparisons with closely related receptors, including RY-amide peptide-recognizing GPCRs, revealed conserved and diversified peptide recognition mechanisms, providing profound insights into the biological significance of RF-amide peptides. Collectively, this study not only advances our understanding of GPCR-ligand interactions, but also paves the way for the development of novel therapeutics targeting metabolic and appetite disorders and emergency medical care.
PubMed: 38897996
DOI: 10.1038/s41467-024-49030-5
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.19 Å)
Structure validation

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