1ljv
From Proteopedia
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Bovine Pancreatic Polypeptide Bound to DPC Micelles
Overview
The pancreatic polypeptide (PP), a 36-residue, C-terminally amidated, polypeptide hormone is a member of the neuropeptide Y (NPY) family. Here, we have studied the structure and dynamics of bovine pancreatic, polypeptide (bPP) when bound to DPC-micelles as a membrane-mimicking model, as well as the dynamics of bPP in solution. The comparison of structure, and dynamics of bPP in both states reveals remarkable differences. The, overall correlation time of 5.08ns derived from the 15N relaxation data, proves unambiguously that bPP in solution exists as a dimer. Therein, intermolecular as well as intramolecular hydrophobic interactions from, residues of both the amphiphilic helix and of the back-folded N terminus, contribute to the stability of the PP fold. The overall rigidity is, well-reflected in positive values for the heteronuclear NOE for residues, 4-34.The membrane-bound species displays a partitioning into a more, flexible N-terminal region and a well-defined alpha-helical region, comprising residues 17-31. The average RMSD value for residues 17-31 is, 0.22(+/-0.09)A. The flexibility of the N terminus is compatible with, negative values of the heteronuclear NOE observed for the N-terminal, residues 4-12 and low values of the generalized order parameter S(2). The, membrane-peptide interface was investigated by micelle-integrating, spin-labels and H,2H exchange measurements. It is formed by those residues, which make contacts between the C-terminal alpha-helix and the polyproline, helix. In contrast to pNPY, also residues from the N terminus display, spatial proximity to the membrane interface. Furthermore, the orientation, of the C terminus, that presumably contains residues involved in receptor, binding, is different in the two environments. We speculate that this, pre-positioning of residues could be an important requirement for receptor, activation. Moreover, we doubt that the PP fold is of functional relevance, for binding at the Y(4) receptor.
About this Structure
1LJV is a Single protein structure of sequence from Bos taurus with NH2 as ligand. Full crystallographic information is available from OCA.
Reference
Bovine pancreatic polypeptide (bPP) undergoes significant changes in conformation and dynamics upon binding to DPC micelles., Lerch M, Gafner V, Bader R, Christen B, Folkers G, Zerbe O, J Mol Biol. 2002 Oct 4;322(5):1117-33. PMID:12367532
Page seeded by OCA on Tue Nov 20 20:36:41 2007
