1RON

NMR SOLUTION STRUCTURE OF HUMAN NEUROPEPTIDE Y

Summary for 1RON

• Entry DOI: 10.2210/pdb1ron/pdb
• Descriptor: NEUROPEPTIDE Y (1 entity in total)
• Functional Keywords: neuropeptide, cleavage on pair of basic residues, amidation, neuromodulator
• Biological source: Homo sapiens (human)
• Cellular location: Secreted: P01303
• Total number of polymer chains: 1
• Total formula weight: 4276.73

Authors

Monks, S.A.,Karagianis, G.,Howlett, G.J.,Norton, R.S. (deposition date: 1996-01-11, release date: 1996-08-17, Last modification date: 2024-11-13)

Primary citation

Monks, S.A.,Karagianis, G.,Howlett, G.J.,Norton, R.S.
Solution structure of human neuropeptide Y.
J.Biomol.NMR, 8:379-390, 1996

PubMed Abstract: The three-dimensional structure of synthetic human neuropeptide Y in aqueous solution at pH 3.2 and 37 degrees C was determined from two-dimensional 1H NMR data recorded at 600 MHz. A restraint set consisting of 440 interproton distance restraints inferred from NOEs and 11 backbone and 4 side-chain dihedral angle restraints derived from spin-spin coupling constants was used as input for distance geometry calculations on DIANA and simulated annealing and restrained energy minimization in X-PLOR. The final set of 26 structures is well defined in the region of residues 11-36, with a mean pairwise rmsd of 0.51 A for the backbone heavy atoms (N, C alpha and C) and 1.34 A for all heavy atoms. Residues 13-36 form an amphipathic alpha-helix. The N-terminal 10 residues are poorly defined relative to the helical region, although some elements of local structure are apparent. At least one of the three prolines in the N-terminal region co-exists in both cis and trans conformations. An additional set of 24 distances was interpreted as intermolecular distances within a dimer. A combination of distance geometry and restrained simulated annealing yielded a model of the dimer having antiparallel packing of two helical units, whose hydrophobic faces form a well-defined core. Sedimentation equilibrium experiments confirm the observation that neuropeptide Y associates to form dimers and higher aggregates under the conditions of the NMR experiments. Our results therefore support the structural features reported for porcine neuropeptide Y [Cowley, D.J. et al. (1992) Eur. J. Biochem., 205, 1099-1106] rather than the 'aPP' fold described previously for human neuropeptide Y [Darbon, H. et al. (1992) Eur. J. Biochem., 209, 765-771].

PubMed: 9008359
DOI: 10.1007/BF00228141

Experimental method

SOLUTION NMR