title: Structural basis of protein oxidation resistance: a lysozyme study.
abstract: Accumulation of oxidative damage in proteins correlates with aging since it can cause irreversible and progressive degeneration of almost all cellular functions. Apparently, native protein structures have evolved intrinsic resistance to oxidation since perfectly folded proteins are, by large most robust. Here we explore the structural basis of protein resistance to radiation-induced oxidation using chicken egg white lysozyme in the native and misfolded form. We study the differential resistance to oxidative damage of six different parts of native and misfolded lysozyme by a targeted tandem/mass spectrometry approach of its tryptic fragments. The decay of the amount of each lysozyme fragment with increasing radiation dose is found to be a two steps process, characterized by a double exponential evolution of their amounts: the first one can be largely attributed to oxidation of specific amino acids, while the second one corresponds to further degradation of the protein. By correlating these results to the structural parameters computed from molecular dynamics (MD) simulations, we find the protein parts with increased root-mean-square deviation (RMSD) to be more susceptible to modifications. In addition, involvement of amino acid side-chains in hydrogen bonds has a protective effect against oxidation Increased exposure to solvent of individual amino acid side chains correlates with high susceptibility to oxidative and other modifications like side chain fragmentation. Generally, while none of the structural parameters alone can account for the fate of peptides during radiation, together they provide an insight into the relationship between protein structure and susceptibility to oxidation.
authors.affiliation: Université de Lyon, 69622, Lyon, France; Institut des Sciences Analytiques, UMR 5280, CNRS, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Girod
authors.affiliation: Université de Lyon, 69622, Lyon, France; Institut Lumière Matière, UMR 5306, CNRS, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Quentin
authors.initials: Q
authors.lastname: Enjalbert
authors.affiliation: Université de Lyon, 69622, Lyon, France; Institut Lumière Matière, UMR 5306, CNRS, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Brunet
authors.affiliation: Université de Lyon, 69622, Lyon, France; Institut Lumière Matière, UMR 5306, CNRS, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Rodolphe
authors.initials: R
authors.lastname: Antoine
authors.affiliation: Université de Lyon, 69622, Lyon, France; Institut des Sciences Analytiques, UMR 5280, CNRS, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lemoine
authors.affiliation: Mediterranean Institute for Life Sciences, Split, Croatia; Liverpool John Moores University, School of Pharmacy and Biomolecular Sciences, Liverpool, Merseyside, England.
authors.forename: Iva
authors.initials: I
authors.lastname: Lukac
authors.affiliation: Mediterranean Institute for Life Sciences, Split, Croatia; INSERM U1001, Faculte de Medecine, Universite R. Descartes Paris-5, Paris, France.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Radman
authors.affiliation: Mediterranean Institute for Life Sciences, Split, Croatia.
authors.forename: Anita
authors.initials: A
authors.lastname: Krisko
authors.affiliation: Université de Lyon, 69622, Lyon, France; Institut Lumière Matière, UMR 5306, CNRS, Université Claude Bernard Lyon 1, Lyon, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Dugourd
mesh_terms: D000595:Amino Acid Sequence; D005720:Gamma Rays; D013058:Mass Spectrometry; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D009113:Muramidase / Q000737:chemistry* / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000528:radiation effects; D017510:Protein Folding; D017434:Protein Structure, Tertiary
chemical_list: C421864:hen egg lysozyme; D009113:Muramidase