Document Detail

Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA carboxylase.
MedLine Citation:
PMID:  16023992     Owner:  NLM     Status:  MEDLINE    
Inherited deficiency of 3-methylcrotonyl-CoA carboxylase (MCC), an enzyme of leucine degradation, is an organic acidemia detectable by expanded newborn screening with a variable phenotype that ranges from asymptomatic to death in infancy. Here, we show that the two subunits of the enzyme (MCCalpha; MCCbeta) are imported into the mitochondrial matrix by the classical pathway involving cleavable amino-terminal targeting presequences. We identified the cleavage sites (Tyr41/Thr42 and Ala22/Tyr23 for MCCalpha and MCCbeta, respectively) of the targeting signals and the amino-termini of the mature polypeptides of MCC and propionyl-CoA carboxylase, a mitochondrial paralog. The amino-termini containing 39 (MCCalpha) or 20 amino acids (MCCbeta) were both necessary and sufficient for targeting. Structural requirements for mitochondrial import were defined by site-directed mutagenesis. Our studies provide the prerequisite to understand the impact of specific mutations on the clinical phenotype of MCC deficiency.
Sonja C Stadler; Roman Polanetz; Stephan Meier; Peter U Mayerhofer; Johannes M Herrmann; Katja Anslinger; Adelbert A Roscher; Wulf Röschinger; Andreas Holzinger
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  334     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-01     Completed Date:  2006-07-05     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  939-46     Citation Subset:  IM    
Dr. von Hauner Children's Hospital, Department of Biochemical Genetics and Molecular Biology, Ludwig-Maximilians-University, Munich, Germany.
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MeSH Terms
Amino Acid Sequence
Carbon-Carbon Ligases / chemistry,  deficiency,  genetics,  metabolism*
Carrier Proteins / metabolism
Kidney / chemistry
Mitochondria / metabolism*
Molecular Sequence Data
Protein Transport / physiology*
Recombinant Fusion Proteins / metabolism
Saccharomyces cerevisiae / metabolism
Reg. No./Substance:
0/Carrier Proteins; 0/Recombinant Fusion Proteins; 0/biotin-binding proteins; EC 6.4.-/Carbon-Carbon Ligases; EC CoA carboxylase (ATP-hydrolyzing); EC carboxylase

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