2IW5

Structural Basis for CoREST-Dependent Demethylation of Nucleosomes by the Human LSD1 Histone Demethylase

Summary for 2IW5

• Entry DOI: 10.2210/pdb2iw5/pdb
• Related: 2COM
• Descriptor: LYSINE-SPECIFIC HISTONE DEMETHYLASE 1, REST COREPRESSOR 1, FLAVIN-ADENINE DINUCLEOTIDE, ... (7 entities in total)
• Functional Keywords: oxidoreductase-transcription regulator complex, oxidoreductase-repressor complex, histone demethylase, fad, lsd1, corest, repressor, transcription regulation, host-virus interaction, chromatin demethylation, nuclear protein, phosphorylation, chromatin regulator, nucleosomes, transcription, oxidoreductase, oxidoreductase/transcription regulator
• Biological source: HOMO SAPIENS (HUMAN); More
• Total number of polymer chains: 2
• Total formula weight: 101646.65

Authors

Yang, M.,Gocke, C.B.,Luo, X.,Borek, D.,Tomchick, D.R.,Machius, M.,Otwinowski, Z.,Yu, H. (deposition date: 2006-06-26, release date: 2006-08-09, Last modification date: 2024-05-08)

Primary citation

Yang, M.,Gocke, C.B.,Luo, X.,Borek, D.,Tomchick, D.R.,Machius, M.,Otwinowski, Z.,Yu, H.
Structural Basis for Corest-Dependent Demethylation of Nucleosomes by the Human Lsd1 Histone Demethylase
Mol.Cell, 23:377-, 2006

PubMed Abstract: Histone methylation regulates diverse chromatin-templated processes, including transcription. Many transcriptional corepressor complexes contain lysine-specific demethylase 1 (LSD1) and CoREST that collaborate to demethylate mono- and dimethylated H3-K4 of nucleosomes. Here, we report the crystal structure of the LSD1-CoREST complex. LSD1-CoREST forms an elongated structure with a long stalk connecting the catalytic domain of LSD1 and the CoREST SANT2 domain. LSD1 recognizes a large segment of the H3 tail through a deep, negatively charged pocket at the active site and possibly a shallow groove on its surface. CoREST SANT2 interacts with DNA. Disruption of the SANT2-DNA interaction diminishes CoREST-dependent demethylation of nucleosomes by LSD1. The shape and dimension of LSD1-CoREST suggest its bivalent binding to nucleosomes, allowing efficient H3-K4 demethylation. This spatially separated, multivalent nucleosome binding mode may apply to other chromatin-modifying enzymes that generally contain multiple nucleosome binding modules.

PubMed: 16885027
DOI: 10.1016/J.MOLCEL.2006.07.012

Experimental method

X-RAY DIFFRACTION (2.57 Å)