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Biochemistry. 2012 Jul 31;51(30):5942-50. Epub 2012 Jul 19.

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

Author information

1
Department of Microbiology, Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.

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.

PMID:
22769851
PMCID:
PMC3447998
DOI:
10.1021/bi300278f
[Indexed for MEDLINE]
Free PMC Article

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