University of Surrey

Test tubes in the lab Research in the ATI Dance Research

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.

Full text not available from this repository.

Abstract

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
Authors :
NameEmailORCID
Stadler, SCUNSPECIFIEDUNSPECIFIED
Polanetz, RUNSPECIFIEDUNSPECIFIED
Meier, SUNSPECIFIEDUNSPECIFIED
Mayerhofer, PUp.mayerhofer@surrey.ac.ukUNSPECIFIED
Herrmann, JMUNSPECIFIEDUNSPECIFIED
Anslinger, KUNSPECIFIEDUNSPECIFIED
Roscher, AAUNSPECIFIEDUNSPECIFIED
Roschinger, WUNSPECIFIEDUNSPECIFIED
Holzinger, AUNSPECIFIEDUNSPECIFIED
Date : 2005
Identification Number : 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 : 17 May 2017 14:51
URI: http://epubs.surrey.ac.uk/id/eprint/828853

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800