6f3v
Backbone structure of bradykinin (BK) peptide bound to human Bradykinin 2 Receptor (B2R) determined by MAS SSNMRBackbone structure of bradykinin (BK) peptide bound to human Bradykinin 2 Receptor (B2R) determined by MAS SSNMR
Structural highlights
Publication Abstract from PubMedG-protein-coupled receptors (GPCRs) are the most important signal transducers in higher eukaryotes. Despite considerable progress, the molecular basis of subtype-specific ligand selectivity, especially for peptide receptors, remains unknown. Here, by integrating DNP-enhanced solid-state NMR spectroscopy with advanced molecular modeling and docking, the mechanism of the subtype selectivity of human bradykinin receptors for their peptide agonists has been resolved. The conserved middle segments of the bound peptides show distinct conformations that result in different presentations of their N and C termini toward their receptors. Analysis of the peptide-receptor interfaces reveals that the charged N-terminal residues of the peptides are mainly selected through electrostatic interactions, whereas the C-terminal segments are recognized via both conformations and interactions. The detailed molecular picture obtained by this approach opens a new gateway for exploring the complex conformational and chemical space of peptides and peptide analogs for designing GPCR subtype-selective biochemical tools and drugs. The molecular basis of subtype selectivity of human kinin G-protein-coupled receptors.,Joedicke L, Mao J, Kuenze G, Reinhart C, Kalavacherla T, Jonker HRA, Richter C, Schwalbe H, Meiler J, Preu J, Michel H, Glaubitz C Nat Chem Biol. 2018 Jan 15. pii: nchembio.2551. doi: 10.1038/nchembio.2551. PMID:29334381[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
|
| ||||||||||||||