title: Lysine methylation modulates the protein-protein interactions of yeast cytochrome C Cyc1p.
abstract: In recent years, protein methylation has been established as a major intracellular PTM. It has also been proposed to modulate protein-protein interactions (PPIs) in the interactome. To investigate the effect of PTMs on PPIs, we recently developed the conditional two-hybrid (C2H) system. With this, we demonstrated that arginine methylation can modulate PPIs in the yeast interactome. Here, we used the C2H system to investigate the effect of lysine methylation. Specifically, we asked whether Ctm1p-mediated trimethylation of yeast cytochrome c Cyc1p, on lysine 78, modulates its interactions with Erv1p, Ccp1p, Cyc2p and Cyc3p. We show that the interactions between Cyc1p and Erv1p, and between Cyc1p and Cyc3p, are significantly increased upon trimethylation of lysine 78. This increase of interaction helps explain the reported facilitation of Cyc1p import into the mitochondrial intermembrane space upon methylation. This first application of the C2H system to the study of methyllysine-modulated interactions further confirms its robustness and flexibility.
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Winter
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Dhanushi
authors.initials: D
authors.lastname: Abeygunawardena
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Gene
authors.initials: G
authors.lastname: Hart-Smith
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Erce
authors.affiliation: Systems Biology Initiative, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Wilkins
mesh_terms: D015153:Blotting, Western; D045304:Cytochromes c / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D008239:Lysine / Q000378:metabolism*; D013058:Mass Spectrometry; D008745:Methylation; D011485:Protein Binding; D020798:Two-Hybrid System Techniques
chemical_list: D045304:Cytochromes c; D008239:Lysine
keywords: Cytochrome c; Lysine methylation; Protein-protein interactions; Systems biology; Two-hybrid