2iw5

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spinqualitylabelsall models 2iw5, resolution 2.57Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

STRUCTURAL BASIS FOR COREST-DEPENDENT DEMETHYLATION OF NUCLEOSOMES BY THE HUMAN LSD1 HISTONE DEMETHYLASE

Overview

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.

About this Structure

2IW5 is a Protein complex structure of sequences from Homo sapiens with , , and as ligands. Known structural/functional Site: . Full crystallographic information is available from OCA.

Reference

Structural basis for CoREST-dependent demethylation of nucleosomes by the human LSD1 histone demethylase., Yang M, Gocke CB, Luo X, Borek D, Tomchick DR, Machius M, Otwinowski Z, Yu H, Mol Cell. 2006 Aug 4;23(3):377-87. PMID:16885027

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