The structure of the neuropeptide bradykinin bound to the human G-protein coupled receptor bradykinin B2 as determined by solid-state NMR spectroscopy

G protein-coupled receptors (GPCRs) are responsible for a large number of physiological processes, such as sensory transduction, mediation of hormonal activity and cell to cell communication. GPCRs are membrane proteins with seven transmembrane helices and are the target of some 50% of today’s modern drugs.  Pharmacological research and rational drug design aimed at GPCRs can be based on homology models derived from X-ray structures but additional data are needed. This limitation could be potentially overcome by determining the structures of bound agonists, which activate GPCRs, and using these as structural templates for drug-design. Solid-state NMR is ideally suited to obtain such structural constraints.

In a recent study, we have determined the backbone structure of the neuropeptide bradykinin bound to the human G-protein coupled bradykinin subtype 2 receptor by solid state NMR. 13C chemical shift based torsion angle constraints were used for structure calculation which revealed an elongated conformation with an alpha-helical turn at the N-terminus and a beta-turn at the C-terminus.

  • Lopez JJ, Shukla AK, Reinhart C, Schwalbe H, Michel H, Glaubitz C. The structure of the neuropeptide bradykinin bound to the human G-protein coupled receptor bradykinin B2 as determined by solid-state NMR spectroscopy. Angew Chem Int Ed Engl.; 47:1668 (2008).