Three dimensional structure of mammalian tachykinin peptide neurokinin B bound to lipid micelles.
Neurokinin B (NKB), a decapeptide of mammalian origin exhibits a variety of biological activities such as regulatory functions in reproduction, pre-eclampsia and neuroprotection in Alzheimer's disease. In order to gain insight into structure-function relationship, three-dimensional structure of NKB has been investigated using CD spectropolarimetry and two-dimensional proton nuclear magnetic resonance (2D 1H-NMR) spectroscopy in aqueous and membrane mimetic solvents. Unambiguous NMR assignments of resonances have been made with the aid of correlation spectroscopy (DQF-COSY and TOCSY) experiments and Nuclear Overhauser Effect Spectroscopy (NOESY) experiments. Distance constraints obtained from the NMR data have been used to generate a family of structures, which have been refined using restrained energy minimization and dynamics. Our data show that a helical structure is induced in NKB, in presence of perdeuterated dodecyl phosphocholine (DPC) micelles, a membrane model system. Further, the conformation adopted by NKB in presence of DPC micelles represents a structural motif typical of neurokinin-3 selective agonists.
School of Life Sciences, Jawaharlal Nehru University, New Delhi--110 067, India.
Anil K
AK
Mantha
Indu R
IR
Chandrashekar
Najma Z
NZ
Baquer
Sudha M
SM
Cowsik
D000595:Amino Acid Sequence; D000818:Animals; D002942:Circular Dichroism; D003903:Deuterium; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008823:Micelles; D008958:Models, Molecular; D015287:Neurokinin B / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular; D010767:Phosphorylcholine / Q000031:analogs & derivatives*; D011487:Protein Conformation; D018042:Receptors, Neurokinin-3 / Q000819:agonists; D013816:Thermodynamics
D008823:Micelles; D018042:Receptors, Neurokinin-3; D010767:Phosphorylcholine; C028810:dodecylphosphocholine; D015287:Neurokinin B; D003903:Deuterium