| Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA carboxylase. | |
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MedLine Citation:
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PMID: 16023992 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Sonja C Stadler; Roman Polanetz; Stephan Meier; Peter U Mayerhofer; Johannes M Herrmann; Katja Anslinger; Adelbert A Roscher; Wulf Röschinger; Andreas Holzinger |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 334 ISSN: 0006-291X ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2005 Sep |
Date Detail:
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Created Date: 2005-08-01 Completed Date: 2006-07-05 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 939-46 Citation Subset: IM |
Affiliation:
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Dr. von Hauner Children's Hospital, Department of Biochemical Genetics and Molecular Biology, Ludwig-Maximilians-University, Munich, Germany. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Sequence Carbon-Carbon Ligases / chemistry, deficiency, genetics, metabolism* Carrier Proteins / metabolism Humans Kidney / chemistry Mitochondria / metabolism* Molecular Sequence Data Protein Transport / physiology* Recombinant Fusion Proteins / metabolism Saccharomyces cerevisiae / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Carrier Proteins; 0/Recombinant Fusion Proteins; 0/biotin-binding proteins; EC 6.4.-/Carbon-Carbon Ligases; EC 6.4.1.3/propionyl CoA carboxylase (ATP-hydrolyzing); EC 6.4.1.4/methylcrotonoyl-CoA carboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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