Revealing the protein propionylation activity of the histone acetyltransferase MOF (males absent on the first)

J Biol Chem. 2018 Mar 2;293(9):3410-3420. doi: 10.1074/jbc.RA117.000529. Epub 2018 Jan 10.

Abstract

Short-chain acylation of lysine residues has recently emerged as a group of reversible posttranslational modifications in mammalian cells. The diversity of acylation further broadens the landscape and complexity of the proteome. Identification of regulatory enzymes and effector proteins for lysine acylation is critical to understand functions of these novel modifications at the molecular level. Here, we report that the MYST family of lysine acetyltransferases (KATs) possesses strong propionyltransferase activity both in vitro and in cellulo Particularly, the propionyltransferase activity of MOF, MOZ, and HBO1 is as strong as their acetyltransferase activity. Overexpression of MOF in human embryonic kidney 293T cells induced significantly increased propionylation in multiple histone and non-histone proteins, which shows that the function of MOF goes far beyond its canonical histone H4 lysine 16 acetylation. We also resolved the X-ray co-crystal structure of MOF bound with propionyl-coenzyme A, which provides a direct structural basis for the propionyltransferase activity of the MYST KATs. Our data together define a novel function for the MYST KATs as lysine propionyltransferases and suggest much broader physiological impacts for this family of enzymes.

Keywords: Males absent on the first (MOF); acetyltransferase; crystal structure; lysine propionylation; post-translational modification (PTM); protein acylation; proteomics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • HEK293 Cells
  • Histone Acetyltransferases / chemistry
  • Histone Acetyltransferases / metabolism*
  • Humans
  • Lysine / metabolism
  • Models, Molecular
  • Protein Conformation
  • Protein Processing, Post-Translational*
  • Proteomics

Substances

  • Histone Acetyltransferases
  • KAT8 protein, human
  • Lysine

Associated data

  • PDB/2GIV
  • PDB/5WCI