1 research outputs found
Substrate Specificity of Mammalian N-Terminal α-Amino Methyltransferase NRMT
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