2MCE

Membrane induced structure of the mammalian tachykinin neuropeptide gamma

Summary for 2MCE

• Entry DOI: 10.2210/pdb2mce/pdb
• NMR Information: BMRB: 19437
• Descriptor: Neuropeptide gamma (1 entity in total)
• Functional Keywords: tachykinin, nk-2 selective agonists, neuropeptide gamma, bioactive peptide, peptide membrane interaction, neuropeptide
• Cellular location: Secreted: P41540
• Total number of polymer chains: 1
• Total formula weight: 2327.62

Authors

Chandrashekar, I.R.,Ganjiwale, A.,Cowsik, S.M. (deposition date: 2013-08-19, release date: 2013-09-25, Last modification date: 2024-05-15)

Primary citation

Chandrashekar, I.R.,Dike, A.,Cowsik, S.M.
Membrane-induced structure of the mammalian tachykinin neuropeptide gamma.
J.Struct.Biol., 148:315-325, 2004

PubMed Abstract: Neuropeptide gamma (NPgamma) is a neurokinin-2 (NK-2) receptor selective agonist, which plays an important role in mediation of asthma and elicits a wide range of biological responses like bronchoconstriction, vasodepression and regulation of endocrine functions. The structure determination of this peptide agonist is important in understanding the molecular basis of peptide ligand recognition by the receptor and for rational drug design. In the present study we report the solution structure of NPgamma characterized by circular dichroism (CD) spectropolarimetry and 2D (1)H NMR spectroscopy in both aqueous and membrane mimetic solvents. Effect of calcium ions on the conformation of NPgamma was also studied using CD spectropolarimetry. Sequence-specific resonance assignments of protons have been made with the aid of correlation spectroscopy experiments and nuclear Overhauser effect spectroscopy experiments. The distance constraints obtained from the NMR data have been utilized to generate a family of structures, which have been refined using restrained energy minimization and dynamics. These data show that in water NPgamma prefers to be in an extended chain conformation whereas a helical conformation is induced in the central core and the C-terminal region of the peptide (K13-M21) in the presence of perdeuterated dodecylphosphocholine micelles, a membrane model system. A type II' beta turn from H9 to R11 precedes the helical core in the C-terminus of NPgamma. N-terminus of NPgamma also displays some degree of order and a possible turn structure. Conformation adopted by NPgamma in presence of lipid micelles represents a structural motif typical of NK-2 selective agonists and is similar to that observed for Neurokinin A in hydrophobic environment. The observed conformational features have been correlated to the binding ability and biological activity of NPgamma.

PubMed: 15522780
DOI: 10.1016/j.jsb.2004.08.008

Experimental method

SOLUTION NMR