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.