Poster Presentation 2014 International Biophysics Congress

Membrane induced structure of novel human tachykinin hemokinin-1 (hHK1) (#318)

Anjali Ganjiwale 1 , Priyanka Mishra 2 , Sudha Cowsik 2
  1. IBAB, Institute of Bioinformatics and Applied Biotechnology, Bangalore, Karnataka, India
  2. Jawaharlal Nehru University, New Delhi, India
PPT-C encoded hemokinin-1 (TGKASQFFGLM) of Homo sapiens is a structurally distinct neuropeptide among the tachykinin family that participate in the NK-1 receptor downstream signaling processes. Subsequently, signal transduction leads to execution of various effecter functions which includes aging, immunological and central nervous system (CNS) regulatory actions. However the conformational pattern of ligand receptor binding is unclear. The three-dimensional structure of the hemokinin-1 in aqueous and micellar environment has been studied by CD Spectroscopy and two-dimensional proton nuclear magnetic resonance (2D 1H-NMR spectroscopy) and distance geometry calculations. CD data shows that hemokinin-1 was unstructured in aqueous environment; anionic detergent SDS induces α-helix formation. Proton NMR assignments have been carried out with the aid of correlation spectroscopy (gradient-COSY and TOCSY) and nuclear Overhauser effect spectroscopy (NOESY and ROESY) experiments. The inter proton distances and dihedral angle constraints obtained from the NMR data have been used in torsion angle dynamics algorithm for NMR applications (CYANA) to generate a family of structures, which have been refined using restrained energy minimization and dynamics. The results show that in aqueous environment hemokinin-1 lacks a definite secondary structure. The structure is well defined in presence of SDS micelles. The conformational range of the peptide revealed by NMR studies has been analyzed in terms of characteristic secondary features. Observed conformational features have been compared to that of Substance P and Physaelamin potent NK1 agonists. Thus the report provides a structural insight to study hHK-1-NK1 interaction that is essential for hHK1 based signaling events.