Yeast cytochrome c-specific protein-lysine methyltransferase: coordinate regulation with cytochrome c and activities in cyc mutants

Abstract

The cytochromes c of fungi and higher plants contain one or two residues of e-N-trimethyllysine, whose biological role is unknown. A cytochrome c-specific Sadenosylmethionine:protein-lysine methyltransferase (methylase) activity was shown to be present in extracts of the bakers' yeast Saccharomyces cerevisiae, and basic kinetic properties of this enzyme are described. The specific activity of the methylase was lower in extracts of cells grown under conditions of catabolite (glucose) repression or anaerobiosis where cytochrome c levels were low, compared with cells grown under derepressed conditions where cytochrome c levels were high. During anaerobic-to-aerobic adaptation, the methylase was induced in parallel with cytochrome c, thus suggestiDng that the syntheses of cytochrome c and cytochrome c methylase are coordinately regulated. None of the cyc strains surveyed (cycl, cyc2, cyc3, cyc4, cyc5, and cyc6) had diminished levels of methylase, although some of them were completely or almost completely deficient in cytochrome c.

Sequence Requirement for Trimethylation of Yeast Cytochromec

“…Furthermore, the activity of the methylase is lower in extracts of yeast grown under conditions of catabolite repression or anaerobiosis, the same conditions where cytochrome c is low. Also, during anaerobic to aerobic adaptation, the methylase was induced with cytochrome c, indicating that the synthesis of cytochrome c and the methylase are at least partially coordinately regulated (Liao & Sherman, 1979). These results suggest that cytochrome c may be the natural and sole substrate.…”

Protein methylation in mitochondria

“…Unlike the other MTases described in this review, which are all 7BS MTases, Ctm1p belongs to the SET-domain class of MTases, which primarily encompasses KMTs involved in histone methylation. Ctm1p is localized to the cytoplasm, indicating that methylation of cytochrome c occurs in the cytoplasm, prior to mitochondrial import ( 102 , 104 ). Apocytochrome c, i.e.…”

Lysine methylation modulates the protein–protein interactions of yeast cytochrome C Cyc1p

“…In Saccharomyces cerevisiae , cytochrome c is expressed from the CYC1 gene and is immediately trimethylated at lysine 78 (often referred to as lysine 72 by homology to vertebrates) by the cytochrome c methyltransferase Ctm1p. Ctm1p is co‐ordinately regulated with Cyc1p . Cyc1p is then localized in the intermembrane space (IMS) of mitochondria where it undergoes a final maturation step, the attachment of a heme c, which is carried out by the cytochrome c heme lyase Cyc3p and flavoprotein Cyc2p .…”