title: Hydrophobic forces are responsible for the folding of a highly potent natriuretic peptide analogue at a membrane mimetic surface: an NMR study.
abstract: A conformational study by nmr spectroscopy was performed with the highly active 28 residue hybrid natriuretic peptide analogue pBNP1 [M. Mimeault, A. De Léan, M. Lafleur, D. Bonenfant, and A. Fournier (1995) Biochemistry, Vol. 34, pp. 955-964], which consists of the cyclic peptide core of pBNP32 and the N- and C-terminal exocyclic segments of rANP (99-126). In purely aqueous solution pBNP1 exhibits random coil behavior as evidenced by the almost complete absence of structurally significant nmr observables. By contrast, elements of secondary structure emerged upon the addition of dodecylphosphocholine micelles to the aqueous sample. Nuclear Overhauser effect distance-restrained molecular dynamics simulations in conjunction with torsional angle determinations permitted the generation of reasonable model of the lipid-bound conformation of pBNP1. According to this model, pBNP1 adopts turn-like features in the cyclic and C-terminal regions of the peptide, but remains quite flexible in the N-terminal segment. Two hydrophobic cores separated by a hydrophilic cleft were also evident in the generated structure. A mechanism is proposed whereby the hydrophobic interactions necessary to stabilize a folded structure of pBNP1 are facilitated by the presence of the membrane-like polar/apolar interface provided by the phospholipid micelles.
authors.affiliation: Laboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, Québec, Canada.
authors.forename: K A
authors.initials: KA
authors.lastname: Carpenter
authors.forename: B C
authors.initials: BC
authors.lastname: Wilkes
authors.forename: A
authors.initials: A
authors.lastname: De Léan
authors.forename: A
authors.initials: A
authors.lastname: Fournier
authors.forename: P W
authors.initials: PW
authors.lastname: Schiller
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000737:chemistry; D001921:Brain / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D020097:Natriuretic Peptide, Brain; D009419:Nerve Tissue Proteins / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D010743:Phospholipids / Q000494:pharmacology; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D051381:Rats; D013552:Swine
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D010455:Peptides; D010743:Phospholipids; D020097:Natriuretic Peptide, Brain; C076910:brain natriuretic peptide, porcine; D009320:Atrial Natriuretic Factor