4GU1

Crystal structure of LSD2

Summary for 4GU1

• Entry DOI: 10.2210/pdb4gu1/pdb
• Related: 4GUR 4GUS 4GUT
• Descriptor: Lysine-specific histone demethylase 1B, FLAVIN-ADENINE DINUCLEOTIDE, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: histone demethylase, oxidoreductase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus (By similarity): Q8NB78
• Total number of polymer chains: 2
• Total formula weight: 178348.96

Authors

Chen, F.,Dong, Z.,Fang, J.,Yang, Y.,Li, Z.,Xu, Y.,Yang, H.,Wang, P.,Fang, R.,Shi, Y.,Xu, Y. (deposition date: 2012-08-29, release date: 2013-01-16, Last modification date: 2023-11-08)

Primary citation

Fang, R.,Chen, F.,Dong, Z.,Hu, D.,Barbera, A.J.,Clark, E.A.,Fang, J.,Yang, Y.,Mei, P.,Rutenberg, M.,Li, Z.,Zhang, Y.,Xu, Y.,Yang, H.,Wang, P.,Simon, M.D.,Zhou, Q.,Li, J.,Marynick, M.P.,Li, X.,Lu, H.,Kaiser, U.B.,Kingston, R.E.,Xu, Y.,Shi, Y.G.
LSD2/KDM1B and its cofactor NPAC/GLYR1 endow a structural and molecular model for regulation of H3K4 demethylation
Mol.Cell, 49:558-570, 2013

PubMed 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 Å, 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.

PubMed: 23260659
DOI: 10.1016/j.molcel.2012.11.019

Experimental method

X-RAY DIFFRACTION (2.939 Å)