Trimethyllysine residues, cytochrome

Monomethyl- and dimethyllysine residues (Fig. 27-29c) occur in some muscle proteins and in cytochrome c. The calmodulin of most species contains one trimethyllysine residue at a specific position. In other proteins, the carboxyl groups of some Glu residues undergo methylation, removing their negative charge. 

Carnitine is synthesized from lysine and methionine by the pathway shown in Figure 14.2 (Vaz and Wanders, 2002). The synthesis of carnitine involves the stepwise methylation of a protein-incorporated lysine residue at the expense of methionine to yield a trimethyllysine residue. Free trimethyllysine is then released by proteolysis. It is not clear whether there is a specific precursor protein for carnitine synthesis, because trimethyllysine occurs in a number of proteins, including actin, calmodulin, cytochrome c, histones, and myosin. 

This protein has been found to be methylated immediately after its synthesis in fungi and higher plants (for a review see Paik, Polastro, and Kim, 1980). The products of the reaction are trimethyllysine residues at positions 72 and 86. The enzyme specific for methylation of lysine-72 has been purified from wheat germ (DiMaria, Kim, and Paik, 1982). Differences between the behavior of methylated and unmethylated cytochrome c suggest that methylation may lead to enhanced mitochondrial import and binding to the mitochondrial inner membrane (Park, Frost, Tuck, Ho, Kim, and Paik, 1987). 

Residue 72 is in a region which is invariant in plant and microbial cytochrome c s and residue 86 is in a region which is characterized in almost all cytochromes as being either Lys-Lys or Lys-Lys-Lys. Neurospora cytochrome c contains c-N-trimethyllysine at residue 72 only, and animal and most plant cytochrome c s are not methylated. 

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