title: Three-dimensional structure of the mammalian tachykinin peptide neurokinin A bound to lipid micelles.
abstract: The solution structure of NKA, a decapeptide of mammalian origin, has been characterized by CD spectropolarimetry and 2D proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy in both aqueous and membrane mimetic solvents. Unambiguous NMR assignments of protons have been made with the aid of correlation spectroscopy (DQF-COSY and TOCSY) experiments and nuclear Overhauser effect spectroscopy (NOESY and ROESY) 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 NKA prefers to be in an extended chain conformation whereas a helical conformation is induced in the central core and the C-terminal region (D4-M10) of the peptide in the presence of perdeuterated dodecylphosphocholine (DPC) micelles, a membrane model system. Though less defined the N-terminus also displays some degree of order and a possible turn structure. The conformation adopted by NKA in the presence of DPC micelles represents a structural motif typical of neurokinin-2 selective agonists and is similar to that reported for eledoisin in hydrophobic environment.
authors.affiliation: School of Life Sciences, Jawaharlal Nehru University, New Delhi 110 067, India.
authors.forename: Indu R
authors.initials: IR
authors.lastname: Chandrashekar
authors.forename: Sudha M
authors.initials: SM
authors.lastname: Cowsik
mesh_terms: D000465:Algorithms; D002462:Cell Membrane / Q000378:metabolism; D002942:Circular Dichroism; D050356:Lipid Metabolism; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D015288:Neurokinin A / Q000737:chemistry* / Q000378:metabolism; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011522:Protons; D018041:Receptors, Neurokinin-2 / Q000737:chemistry; D015320:Tachykinins / Q000737:chemistry*
chemical_list: D008823:Micelles; D011522:Protons; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; D010767:Phosphorylcholine; C028810:dodecylphosphocholine; D015288:Neurokinin A