Lysine 43 is trimethylated in subunit C from bovine mitochondrial ATP synthase and in storage bodies associated with batten disease.

TitleLysine 43 is trimethylated in subunit C from bovine mitochondrial ATP synthase and in storage bodies associated with batten disease.
Publication TypeJournal Article
Year of Publication2004
AuthorsChen, R, Fearnley, IM, Palmer, DN, Walker, JE
JournalJ Biol Chem
Volume279
Issue21
Pagination21883-7
Date Published2004 May 21
ISSN0021-9258
KeywordsAmino Acid Sequence, Animals, Cattle, DNA Methylation, Electrophoresis, Polyacrylamide Gel, Humans, Lysine, Mass Spectrometry, Mitochondria, Mitochondrial Proton-Translocating ATPases, Molecular Sequence Data, Neuronal Ceroid-Lipofuscinoses, Peptides, Protein Processing, Post-Translational, Protein Structure, Secondary, Protein Structure, Tertiary, Sheep, Spectrometry, Mass, Electrospray Ionization, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Abstract

The hydrophobic membrane protein, subunit c, has been isolated from ATP synthase purified from bovine heart mitochondria. It has also been obtained from lysosomal storage bodies associated with ceroid lipofuscinosis from ovine liver and from human brain tissue of a victim of Batten disease. It is likely that the lysosomal protein has originated from the mitochondrion. These samples have been characterized by mass spectrometric methods. Irrespective of its source, subunit c has an intact molecular mass of 7650 Da, 42 Da greater than the value calculated from the amino acid sequence, and the protein has been modified post-translationally. In all three samples, the modification is associated with lysine 43, which lies in a polar loop region linking the two transmembrane alpha-helices of the protein. This residue is conserved throughout vertebrate sequences. The additional mass arises from trimethylation and not acetylation at the epsilon-N-position of the residue. These experiments show that the post-translational modification of subunit c is not, as has been suggested, an abnormal phenomenon associated with the etiology of Batten disease and ceroid lipofucinoses. Evidently, it occurs either before or during import of the protein into mitochondria or at a mitochondrial location after completion of the import process. The function of the trimethyllysine residue in the assembled ATP synthase complex is obscure. The residue and the modification are not conserved in all ATP synthases, and their role in the assembly and (or) functioning of the enzyme appear to be confined to higher organisms.

DOI10.1074/jbc.M402074200
Alternate JournalJ. Biol. Chem.
Citation Key10.1074/jbc.M402074200
PubMed ID15010464