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

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

Author information

1
From the Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602.
2
the Structural Genomics Consortium, University of Toronto, Toronto, Ontario M5G 1L7, Canada.
3
the Ben May Department for Cancer Research, University of Chicago, Chicago, Illinois 60637.
4
the Goodman Cancer Research Center and Department of Medicine, McGill University, Montreal, Quebec H3A 1A3, Canada, and.
5
the Princess Margaret Cancer Centre and Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2M9, Canada.
6
From the Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, Georgia 30602, yzheng@uga.edu.

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

PMID:
29321206
PMCID:
PMC5836141
DOI:
10.1074/jbc.RA117.000529
[Indexed for MEDLINE]
Free PMC Article

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