title: Membrane structure and interactions of human catestatin by multidimensional solution and solid-state NMR spectroscopy.
abstract: Catestatin is a natural peptide of higher organisms including humans, with a wide variety of biological functions involved in catecholamine inhibition, cardiovascular regulation, control of blood pressure, inflammation, and innate immunity. It is derived from the natural processing of chromogranin A, induced in the skin after injury, and produced by chromaffin cells and neutrophils. With neutrophils, the peptide enters the cell by crossing the plasma membrane where it interacts with internal targets to induce calcium influx. Therefore, we investigated the membrane interactions and structure of several catestatin-derived peptides. Whereas fluorescence dye release experiments are indicative of membrane permeabilization, multidimensional solution NMR and circular dichroism spectroscopies show that catestatin adopts alpha-helical conformations between Ser-6 and Tyr-12 in the presence of dodecylphosphocholine micelles. Furthermore, proton-decoupled (15)N solid-state NMR spectroscopy of sequences labeled with (15)N and reconstituted into oriented lipid bilayers indicates that this domain is aligned in a strongly tilted to inplanar alignment. Proton-decoupled (31)P NMR spectra of the same samples are indicative of conformational and/or orientational heterogeneity at the level of the lipid bilayer head groups due to the presence of catestatin. The sequence and 3-dimensional structure of catestatin exhibit homologies with penetratin, which is suggestive that they both enter the cells by related mechanisms to target internal structures.
authors.affiliation: Université de Strasbourg/Centre National de la Recherche Scientifique, UMR 7177, Institut de Chimie, Strasbourg, France.
authors.forename: Masae
authors.initials: M
authors.lastname: Sugawara
authors.forename: Jarbas M
authors.initials: JM
authors.lastname: Resende
authors.forename: Cléria Mendonça
authors.initials: CM
authors.lastname: Moraes
authors.forename: Arnaud
authors.initials: A
authors.lastname: Marquette
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Chich
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Metz-Boutigue
authors.forename: Burkhard
authors.initials: B
authors.lastname: Bechinger
mesh_terms: D000595:Amino Acid Sequence; D053379:Chromogranin A / Q000737:chemistry* / Q000378:metabolism*; D002942:Circular Dichroism; D006801:Humans; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D053379:Chromogranin A; D008051:Lipid Bilayers; D010446:Peptide Fragments; C109084:chromogranin A (344-364)