title: Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene. A predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson's disease.
abstract: Mitochondrial targeting sequence (MTS) has a common property to form an amphiphilic helical structure which is essential for its effective transport of mitochondrial protein. Natural polymorphism in human MTS which affects its mitochondrial transport ability has not been reported. Furthermore, no structural polymorphism for manganese superoxide dismutase (MnSOD) gene has been studied in human population. We here identify diallelic polymorphism (Ala-9Val) in the MTS of human MnSOD in a Japanese population. Calculation of a helix forming potential predicted the typical amphiphilic helical structure in -9Ala allele and its disruption in -9Val allele. We here suggest that this mutation may reflect functional polymorphism of mitochondrial transport of human MnSOD. An association study using this polymorphism showed significant allelic deviation for -9Ala allele (12.1% vs. 19.3%) in Parkinson's disease.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Shimoda-Matsubayashi
authors.forename: H
authors.initials: H
authors.lastname: Matsumine
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakagawa-Hattori
authors.forename: Y
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Y
authors.initials: Y
authors.lastname: Mizuno
mesh_terms: D000368:Aged; D001483:Base Sequence; D001692:Biological Transport; D017931:DNA Primers; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism; D011110:Polymorphism, Genetic; D021382:Protein Sorting Signals / Q000235:genetics*; D017433:Protein Structure, Secondary; D013482:Superoxide Dismutase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D017931:DNA Primers; D021382:Protein Sorting Signals; D013482:Superoxide Dismutase