Conservation of complete trimethylation of lysine-43 in the rotor ring of c-subunits of metazoan adenosine triphosphate (ATP) synthases.

TitleConservation of complete trimethylation of lysine-43 in the rotor ring of c-subunits of metazoan adenosine triphosphate (ATP) synthases.
Publication TypeJournal Article
Year of Publication2015
AuthorsWalpole, TB, Palmer, DN, Jiang, H, Ding, S, Fearnley, IM, Walker, JE
JournalMol Cell Proteomics
Volume14
Issue4
Pagination828-40
Date Published2015 Apr
ISSN1535-9484
KeywordsAmino Acid Sequence, Animals, Conserved Sequence, Humans, Invertebrates, Lysine, Methylation, Molecular Sequence Data, Molecular Weight, Peptides, Phylogeny, Protein Processing, Post-Translational, Protein Subunits, Proton-Translocating ATPases, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry
Abstract

The rotors of ATP synthases turn about 100 times every second. One essential component of the rotor is a ring of hydrophobic c-subunits in the membrane domain of the enzyme. The rotation of these c-rings is driven by a transmembrane proton-motive force, and they turn against a surface provided by another membrane protein, known as subunit a. Together, the rotating c-ring and the static subunit a provide a pathway for protons through the membrane in which the c-ring and subunit a are embedded. Vertebrate and invertebrate c-subunits are well conserved. In the structure of the bovine F1-ATPase-c-ring subcomplex, the 75 amino acid c-subunit is folded into two transmembrane α-helices linked by a short loop. Each bovine rotor-ring consists of eight c-subunits with the N- and C-terminal α-helices forming concentric inner and outer rings, with the loop regions exposed to the phospholipid head-group region on the matrix side of the inner membrane. Lysine-43 is in the loop region and its ε-amino group is completely trimethylated. The role of this modification is unknown. If the trimethylated lysine-43 plays some important role in the functioning, assembly or degradation of the c-ring, it would be expected to persist throughout vertebrates and possibly invertebrates also. Therefore, we have carried out a proteomic analysis of c-subunits across representative species from different classes of vertebrates and from invertebrate phyla. In the twenty-nine metazoan species that have been examined, the complete methylation of lysine-43 is conserved, and it is likely to be conserved throughout the more than two million extant metazoan species. In unicellular eukaryotes and prokaryotes, when the lysine is conserved it is unmethylated, and the stoichiometries of c-subunits vary from 9-15. One possible role for the trimethylated residue is to provide a site for the specific binding of cardiolipin, an essential component of ATP synthases in mitochondria.

DOI10.1074/mcp.M114.047456
Alternate JournalMol. Cell Proteomics
Citation Key10.1074/mcp.M114.047456
PubMed ID25608518
PubMed Central IDPMC4390263
Grant ListMC_U105663148 / / Medical Research Council / United Kingdom
MC_U105663150 / / Medical Research Council / United Kingdom
/ / Medical Research Council / United Kingdom