4GUT: Crystal Structure Of Lsd2-npac

Citation:
Abstract
Dynamic regulation of histone methylation represents a fundamental epigenetic mechanism underlying eukaryotic gene regulation, yet little is known about how the catalytic activities of histone demethylases are regulated. Here, we identify and characterize NPAC/GLYR1 as an LSD2/KDM1b-specific cofactor that stimulates H3K4me1 and H3K4me2 demethylation. We determine the crystal structures of LSD2 alone and LSD2 in complex with the NPAC linker region in the absence or presence of histone H3 peptide, at resolutions of 2.9, 2.0, and 2.25 A, respectively. These crystal structures and further biochemical characterization define a dodecapeptide of NPAC (residues 214-225) as the minimal functional unit for its cofactor activity and provide structural determinants and a molecular mechanism underlying the intrinsic cofactor activity of NPAC in stimulating LSD2-catalyzed H3K4 demethylation. Thus, these findings establish a model for how a cofactor directly regulates histone demethylation and will have a significant impact on our understanding of catalytic-activity-based epigenetic regulation.
PDB ID: 4GUTDownload
MMDB ID: 106751
PDB Deposition Date: 2012/8/29
Updated in MMDB: 2013/07
Experimental Method:
x-ray diffraction
Resolution: 2  Å
Source Organism:
Similar Structures:
Biological Unit for 4GUT: dimeric; determined by author and by software (PISA)
Molecular Components in 4GUT
Label Count Molecule
Proteins (2 molecules)
1
Lysine-specific Histone Demethylase 1B(Gene symbol: KDM1B)
Molecule annotation
1
Putative Oxidoreductase Glyr1(Gene symbol: GLYR1)
Molecule annotation
Chemicals (7 molecules)
1
1
2
2
3
3
4
1
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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