Journal of Biological Chemistry
Volume 289, Issue 44, 31 October 2014, Pages 30499-30510
Journal home page for Journal of Biological Chemistry

Enzymology
Identification and Characterization of a Novel Evolutionarily Conserved Lysine-specific Methyltransferase Targeting Eukaryotic Translation Elongation Factor 2 (eEF2)*

https://doi.org/10.1074/jbc.M114.601658Get rights and content
Under a Creative Commons license
open access

The components of the cellular protein translation machinery, such as ribosomal proteins and translation factors, are subject to numerous post-translational modifications. In particular, this group of proteins is frequently methylated. However, for the majority of these methylations, the responsible methyltransferases (MTases) remain unknown. The human FAM86A (family with sequence similarity 86) protein belongs to a recently identified family of protein MTases, and we here show that FAM86A catalyzes the trimethylation of eukaryotic elongation factor 2 (eEF2) on Lys-525. Moreover, we demonstrate that the Saccharomyces cerevisiae MTase Yjr129c, which displays sequence homology to FAM86A, is a functional FAM86A orthologue, modifying the corresponding residue (Lys-509) in yeast eEF2, both in vitro and in vivo. Finally, Yjr129c-deficient yeast cells displayed phenotypes related to eEF2 function (i.e. increased frameshifting during protein translation and hypersensitivity toward the eEF2-specific drug sordarin). In summary, the present study establishes the function of the previously uncharacterized MTases FAM86A and Yjr129c, demonstrating that these enzymes introduce a functionally important lysine methylation in eEF2. Based on the previous naming of similar enzymes, we have redubbed FAM86A and Yjr129c as eEF2-KMT and Efm3, respectively.

Cited by (0)

*

Research in the laboratory of P. Ø. F. is supported by the University of Oslo and by grants from the Norwegian Cancer Society and the Research Council of Norway.

1

Recipient of a Leverhulme Trust Early Career Fellowship.

3

The abbreviations used are:

    MTase

    methyltransferase

    eEF2

    eukaryotic translation elongation factor 2

    eEF1A

    eukaryotic translation elongation factor 1A

    7BS

    seven-stranded β-sheet

    MTF16

    methyltransferase family 16

    KMT

    lysine methyltransferase

    AdoMet

    S-adenosyl-l-methionine

    CBP

    calmodulin binding peptide

    SBP

    streptavidin binding peptide

    TAP

    tandem affinity purification

    AdoHcy

    S-adenosyl-l-homocysteine

    AdOx

    adenosine dialdehyde

    VCP

    valosin-containing protein.