title: Lunasin is a redox sensitive intrinsically disordered peptide with two transiently populated α-helical regions.
abstract: Lunasin is a 43 amino acid peptide with anti-cancer, antioxidant, anti-inflammatory and cholesterol-lowering properties. Although the mechanism of action of lunasin has been characterized to some extent, its exact three-dimensional structure as well as the function of the N-terminal sequence remains unknown. We established a novel method for the production of recombinant lunasin that allows efficient isotope labeling for NMR studies. Initial studies showed that lunasin can exist in a reduced or oxidized state with an intramolecular disulfide bond depending on solution conditions. The structure of both forms of the peptide at pH 3.5 and 6.5 was characterized by CD spectroscopy and multidimensional NMR methods. The data indicate that lunasin belongs to the class of intrinsically disordered proteins. The analysis of secondary structure propensities indicates the presence of two helical regions and an extended (beta strand) conformation at the C-terminus. We hypothesize that the transient secondary structure elements could be stabilized upon interaction with the histones H3 and H4. The newly discovered redox properties of lunasin could explain its antioxidant and anti-inflammatory activity.
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia.
authors.forename: Rihards
authors.initials: R
authors.lastname: Aleksis
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia.
authors.forename: Kristaps
authors.initials: K
authors.lastname: Jaudzems
authors.affiliation: Faculty of Medicine, University of Latvia, 19 Raina Blvd, Riga, LV-1586, Latvia.
authors.forename: Ruta
authors.initials: R
authors.lastname: Muceniece
authors.affiliation: Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga LV-1006, Latvia. Electronic address: edv@osi.lv.
authors.forename: Edvards
authors.initials: E
authors.lastname: Liepinsh
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence / Q000235:genetics; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000627:therapeutic use; D000975:Antioxidants / Q000737:chemistry* / Q000627:therapeutic use; D004220:Disulfides / Q000737:chemistry; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010940:Plant Proteins / Q000737:chemistry* / Q000378:metabolism; D000072756:Protein Conformation, alpha-Helical; D030262:Soybean Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000975:Antioxidants; D004220:Disulfides; D006657:Histones; D064267:Intrinsically Disordered Proteins; D010455:Peptides; D010940:Plant Proteins; D030262:Soybean Proteins; C556331:lunasin protein, barley
keywords: Cysteine oxidation; Lunasin; NMR spectroscopy; Solution structure