Lipid-induced conformation of substance P.
Both the aqueous and the lipid-induced structure of a representative and widely studied tachykinin, substance P, has been investigated by two-dimensional proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy and distance geometry calculations. Unambiguous NMR assignments of protons have been made with the aid of correlation spectroscopy (COSY and TOCSY) experiments and Overhauser enhancement spectroscopy (ROESY and NOESY; experiments. The NMR data obtained were utilized in a distance geometry algorithm to generate a family of structures which were further refined using restrained energy minimization. These data show that, while in water substance P appears to favour an extended chain conformation, in the presence of perdeuterated dodecylphosphocholine (DPC) micelles as membrane model system an amphiphilic helical conformation is induced in the mid-region (Q5-Q8) of substance P. The conformation adopted by substance P in the presence of DPC micelles yields a structural motif typical of neurokinin-1 selective ligands, as proposed by Convert and coworkers (O. Convert et al., Neuropeptides 19, 259-270 (1991)).
Cowsik
S M
SM
School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
Lücke
C
C
Rüterjans
H
H
D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011522:Protons; D013373:Substance P / Q000737:chemistry*
D008055:Lipids; D008823:Micelles; D011522:Protons; D013373:Substance P