title: Three-dimensional reconstruction of the S885A mutant of human mitochondrial Lon protease.
abstract: The Lon protein is a protease belonging to the superfamily of ATPases associated with diverse cellular activities (AAA+). Its main function is the control of protein quality and the maintenance of proteostasis by degradation of misfolded and damaged proteins, which occur in response to numerous stress conditions. It also participates in the regulation of levels of transcription factors that control pathogenesis, development and stress response. We focus our interest on the structure of human mitochondrial Lon (hLon) protease, whose altered expression levels are linked to some severe diseases such as epilepsy, myopathy, or lateral sclerosis. We present the first 3D structure of the ADP-bound human Lon S885A mutant obtained by electron microscopy as a result of preliminary negative staining studies. S885A appears as a hexameric ring of 120 Å diameter having 90 Å in height. Its resolution was estimated at 19 Å by the FSC = 0.5 criterion. This model is a primary step towards the understanding of the mechanism of action of the Lon protease and its involvement in the pathogenesis development.
authors.affiliation: Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors.forename: S
authors.initials: S
authors.lastname: Kereïche
authors.affiliation: Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Kováčik
authors.affiliation: Department of Biochemistry and Structural Biology, Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: V
authors.initials: V
authors.lastname: Pevala
authors.affiliation: Department of Biochemistry and Structural Biology, Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: L
authors.initials: L
authors.lastname: Ambro
authors.affiliation: Department of Biochemistry and Structural Biology, Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: J
authors.initials: J
authors.lastname: Bellová
authors.affiliation: Department of Biochemistry and Structural Biology, Institute of Molecular Biology, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: E
authors.initials: E
authors.lastname: Kutejová
authors.affiliation: Institute of Cellular Biology and Pathology, First Faculty of Medicine, Charles University in Prague, Czech Republic.
authors.forename: I
authors.initials: I
authors.lastname: Raška
mesh_terms: D006801:Humans; D021621:Imaging, Three-Dimensional; D008928:Mitochondria / Q000201:enzymology*; D008958:Models, Molecular; D050505:Mutant Proteins / Q000737:chemistry*; D016624:Negative Staining; D049070:Protease La / Q000737:chemistry* / Q000648:ultrastructure
chemical_list: D050505:Mutant Proteins; D049070:Protease La