title: Myosin as a potential redox-sensor: an in vitro study.
abstract: A balanced redox status is necessary to optimize force production in contractile apparatus, where free radicals generated by skeletal muscle are involved in some basic physiological processes like excitation-contraction coupling. Protein glutathionylation has a key role in redox regulation of proteins and signal transduction. Here we show that myosin is sensitive to in vitro glutathionylation and MALDI-TOF analysis identified three potential sites of glutathione binding, two of them locating on the myosin head. Glutathionylation of myosin has an important impact on the protein structure, as documented by the lower fluorescence quantum yield of glutathionylated myosin and its increased susceptibility to the proteolytic cleavage. Myosin function is also sensitive to glutathionylation, which modulates its ATPase activity depending on GSSG redox balance. Thus, like the phosphorylation/dephosphorylation cycle, glutathionylation may represent a mechanism by which glutathione modulates sarcomere functions depending on the tissue redox state, and myosin may constitute a muscle redox-sensor.
authors.affiliation: Molecular Medicine Unit, Children's Hospital and Research Institute Bambino Gesù, Department of Biology, University of Rome Roma Tre, P.za S. Onofrio, 4, Rome, 00165, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Passarelli
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrini
authors.forename: Anna
authors.initials: A
authors.lastname: Pastore
authors.forename: Valentina
authors.initials: V
authors.lastname: Bonetto
authors.forename: Patrizio
authors.initials: P
authors.lastname: Sale
authors.forename: Laura M
authors.initials: LM
authors.lastname: Gaeta
authors.forename: Giulia
authors.initials: G
authors.lastname: Tozzi
authors.forename: Enrico
authors.initials: E
authors.lastname: Bertini
authors.forename: Monica
authors.initials: M
authors.lastname: Canepari
authors.forename: Rosetta
authors.initials: R
authors.lastname: Rossi
authors.forename: Fiorella
authors.initials: F
authors.lastname: Piemonte
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002384:Catalysis / Q000187:drug effects; D004229:Dithiothreitol / Q000737:chemistry / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D019803:Glutathione Disulfide / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D009218:Myosins / Q000737:chemistry* / Q000302:isolation & purification / Q000378:metabolism; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000378:metabolism; D011487:Protein Conformation; D051381:Rats; D013050:Spectrometry, Fluorescence; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism; D014357:Trypsin / Q000737:chemistry / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D013438:Sulfhydryl Compounds; D014357:Trypsin; D000251:Adenosine Triphosphatases; D009218:Myosins; D005978:Glutathione; D004229:Dithiothreitol; D019803:Glutathione Disulfide
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