ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Mapping spatial approximations between the amino terminus of secretin and each of the extracellular loops of its receptor using cysteine trapping.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Impact of secretin receptor homo-dimerization on natural ligand binding.Nature communications · 2024Article
- Secretin Amino-Terminal Structure-Activity Relationships and Complementary Mutagenesis at the Site of Docking to the Secretin Receptor.Molecular pharmacology · 2022Article
- Genetically incorporated crosslinkers reveal NleE attenuates host autophagy dependent on PSMD10.eLife · 2021Article
- Structures of the human cholecystokinin 1 (CCK1) receptor bound to Gs and Gq mimetic proteins provide insight into mechanisms of G protein selectivity.PLoS biology · 2021Article
- Capturing Peptide-GPCR Interactions and Their Dynamics.Molecules (Basel, Switzerland) · 2020Review
- Structure and dynamics of the active Gs-coupled human secretin receptor.Nature communications · 2020Article
- Spirohexene-Tetrazine Ligation Enables Bioorthogonal Labeling of Class B G Protein-Coupled Receptors in Live Cells.Journal of the American Chemical Society · 2017Article
- Structural Determinants of Binding the Seven-transmembrane Domain of the Glucagon-like Peptide-1 Receptor (GLP-1R).The Journal of biological chemistry · 2016Article
- The Extracellular Surface of the GLP-1 Receptor Is a Molecular Trigger for Biased Agonism.Cell · 2016Article
- Use of Cysteine Trapping to Map Spatial Approximations between Residues Contributing to the Helix N-capping Motif of Secretin and Distinct Residues within Each of the Extracellular Loops of Its Receptor.The Journal of biological chemistry · 2016Article
- Disulfide Trapping for Modeling and Structure Determination of Receptor: Chemokine Complexes.Methods in enzymology · 2016Article
- Conformational states of the full-length glucagon receptor.Nature communications · 2015Article
- Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors.Frontiers in pharmacology · 2015Review
- Experiment-Guided Molecular Modeling of Protein-Protein Complexes Involving GPCRs.Methods in molecular biology (Clifton, N.J.) · 2015Article
- Structural and functional insights into the juxtamembranous amino-terminal tail and extracellular loop regions of class B GPCRs.British journal of pharmacology · 2014Review
- Computational identification of novel natural inhibitors of glucagon receptor for checking type II diabetes mellitus.BMC bioinformatics · 2014Article
- Insights into the structure of class B GPCRs.Trends in pharmacological sciences · 2014Review
- Article
- The role of ECL2 in CGRP receptor activation: a combined modelling and experimental approach.Journal of the Royal Society, Interface · 2013Article
- Article
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10 authors.
Funding
Abstract
While it is evident that the carboxyl-terminal region of natural peptide ligands bind to the amino-terminal domain of class B GPCRs, how their biologically critical amino-terminal regions dock to the receptor is unclear. We utilize cysteine trapping to systematically explore spatial approximations among residues in the first five positions of secretin and in every position within the receptor extracellular loops (ECLs). Only Cys(2) and Cys(5) secretin analogues exhibited full activity and retained moderate binding affinity (IC(50): 92±4 and 83±1 nM, respectively). When these peptides probed 61 human secretin receptor cysteine-replacement mutants, a broad network of receptor residues could form disulfide bonds consistent with a dynamic ligand-receptor interface. Two distinct patterns of disulfide bond formation were observed: Cys(2) predominantly labeled residues in the amino terminus of ECL2 and ECL3 (relative labeling intensity: Ser(340), 94±7%; Pro(341), 84±9%; Phe(258), 73±5%; Trp(274) 62±8%), and Cys(5) labeled those in the carboxyl terminus of ECL2 and ECL3 (Gln(348), 100%; Ile(347), 73±12%; Glu(342), 59±10%; Phe(351), 58±11%). These constraints were utilized in molecular modeling, providing improved understanding of the structure of the transmembrane bundle and interconnecting loops, the orientation between receptor domains, and the molecular basis of ligand docking. Key spatial approximations between peptide and receptor predicted by this model (H(1)-W(274), D(3)-N(268), G(4)-F(258)) were supported by mutagenesis and residue-residue complementation studies.
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