Journal
JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 285, Issue 52, Pages 40879-40890Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M110.134312
Keywords
-
Categories
Funding
- Saskatchewan Health Research Foundation
- University of Saskatchewan College of Medicine
- Canadian Institutes for Health Research (CIHR) [MOP 79377]
- National Science and Engineering Council of Canada (NSERC)
- Canadian foundation for innovation (CFI)
- University of Saskatchewan
Ask authors/readers for more resources
We have determined the human male specific lethal 3 (hMSL3) chromo-barrel domain structure by x-ray crystallography to a resolution of 2.5 angstrom (r = 0.226, R-free = 0.270). hMSL3 contains a canonical methyllysine binding pocket made up of residues Tyr-31, Phe-56, Trp-59, and Trp-63. A six-residue insertion between strands beta(1) and beta(2) of the hMSL3 chromo-barrel domain directs the side chain of Glu-21 into the methyllysine binding pocket where it hydrogen bonds to the NH group of a bound cyclohexylamino ethanesulfonate buffer molecule, likely mimicking interactions with a histone tail dimethyllysine residue. In vitro binding studies revealed that both the human and Drosophila MSL3 chromo-barrel domains bind preferentially to peptides representing the mono or dimethyl isoform of lysine 20 on the histone H4 N-terminal tail (H4K20Me(1) or H4K20Me(2)). Mutation of Tyr-31 to Ala in the hMSL3 methyllysine-binding cage resulted in weaker in vitro binding to H4K20Me(1). The same mutation in the msl3 gene compromised male survival in Drosophila. Combined mutation of Glu-21 and Pro-22 to Ala in hMSL3 resulted in slightly weaker in vitro binding to H4K20Me(1), but the corresponding msl3 mutation had no effect on male survival in Drosophila. We propose MSL3 plays an important role in targeting the male specific lethal complex to chromatin in both humans and flies by binding to H4K20Me(1). Binding studies on the related dMRG15 chromo-barrel domain revealed that MRG15 prefers binding to H4K20Me(3).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available