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

Mitochondrial targeting sequence (MTS) has a common property to form an amphiphilic helical structure which is essential for its effective transport of mitochonmdrial protein. Natural polymorphism in human MTS which affects its mitochondrial transport ability has not been reported. Furthermore, no s...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1996-09, Vol.226 (2), p.561-565
Main Authors: Shimoda-Matsubayashi, Satoe, Matsumine, Hiroto, Kobayashi, Tomonori, Nakagawa-Hattori, Yuko, Shimizu, Yumiko, Mizuno, Yoshikuni
Format: Article
Language:English
Subjects:
Aged
Base Sequence
Biological Transport
DNA Primers
Humans
Middle Aged
Mitochondria - metabolism
Molecular Sequence Data
Oxidative Stress
Parkinson Disease - metabolism
Polymorphism, Genetic
Protein Sorting Signals - genetics
Protein Structure, Secondary
Superoxide Dismutase - chemistry
Superoxide Dismutase - genetics
Superoxide Dismutase - metabolism
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Summary:Mitochondrial targeting sequence (MTS) has a common property to form an amphiphilic helical structure which is essential for its effective transport of mitochonmdrial 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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.1996.1394