Substrate specificity of mammalian N-terminal α-amino methyltransferase NRMT

Janusz J. Petkowski, Christine E. Schaner Tooley, Lissa C. Anderson, Igor A. Shumilin, Jeremy L. Balsbaugh, Jeffrey Shabanowitz, Donald F. Hunt, Wladek Minor, Ian G. MacAra

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

N-Terminal methylation of free α-amino groups is a post-translational modification of proteins that was first described 30 years ago but has been studied very little. In this modification, the initiating M residue is cleaved and the exposed α-amino group is mono-, di-, or trimethylated by NRMT, a recently identified N-terminal methyltransferase. Currently, all known eukaryotic α-amino-methylated proteins have a unique N-terminal motif, M-X-P-K, where X is A, P, or S. NRMT can also methylate artificial substrates in vitro in which X is G, F, Y, C, M, K, R, N, Q, or H. Methylation efficiencies of N-terminal amino acids are variable with respect to the identity of X. Here we use in vitro peptide methylation assays and substrate immunoprecipitations to show that the canonical M-X-P-K methylation motif is not the only one recognized by NRMT. We predict that N-terminal methylation is a widespread post-translational modification and that there is interplay between N-terminal acetylation and N-terminal methylation. We also use isothermal calorimetry experiments to demonstrate that NRMT can efficiently recognize and bind to its fully methylated products.

Original languageEnglish
Pages (from-to)5942-5950
Number of pages9
JournalBiochemistry
Volume51
Issue number30
DOIs
StatePublished - 31 Jul 2012
Externally publishedYes

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