6F3V

Backbone structure of bradykinin (BK) peptide bound to human Bradykinin 2 Receptor (B2R) determined by MAS SSNMR

6F3V の概要

• エントリーDOI: 10.2210/pdb6f3v/pdb
• NMR情報: BMRB: 34206
• 分子名称: Bradykinin (BK) (1 entity in total)
• 機能のキーワード: gpcr, membrane protein
• 由来する生物種: Homo sapiens
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1062.22

構造登録者

Mao, J.,Lopez, J.J.,Shukla, A.K.,Kuenze, G.,Meiler, J.,Schwalbe, H.,Michel, H.,Glaubitz, C. (登録日: 2017-11-29, 公開日: 2018-01-10, 最終更新日: 2024-06-19)

主引用文献

Joedicke, L.,Mao, J.,Kuenze, G.,Reinhart, C.,Kalavacherla, T.,Jonker, H.R.A.,Richter, C.,Schwalbe, H.,Meiler, J.,Preu, J.,Michel, H.,Glaubitz, C.
The molecular basis of subtype selectivity of human kinin G-protein-coupled receptors.
Nat. Chem. Biol., 14:284-290, 2018

PubMed Abstract: G-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.

PubMed: 29334381
DOI: 10.1038/nchembio.2551

実験手法

SOLID-STATE NMR