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Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA carboxylase

Stadler, SC, Polanetz, R, Meier, S, Mayerhofer, PU, Herrmann, JM, Anslinger, K, Roscher, AA, Roschinger, W and Holzinger, A (2005) Mitochondrial targeting signals and mature peptides of 3-methylcrotonyl-CoA carboxylase Biochem Biophys Res Commun, 334. pp. 939-946.

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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.

Item Type: Article
Divisions : Surrey research (other units)
Authors :
Stadler, SC
Polanetz, R
Meier, S
Herrmann, JM
Anslinger, K
Roscher, AA
Roschinger, W
Holzinger, A
Date : 2005
DOI : 10.1016/j.bbrc.2005.06.190
Uncontrolled Keywords : 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
Related URLs :
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:42
Last Modified : 24 Jan 2020 19:53

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