6z2k

The structure of the tetrameric HDAC1/MIDEAS/DNTTIP1 MiDAC deacetylase complex

spinqualitylabelsall models 6z2k, resolution 4.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6z2k is a 12 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 4.5Å Ligands: IHP, K, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function HDAC1_HUMAN Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes. Deacetylates SP proteins, SP1 and SP3, and regulates their function. Component of the BRG1-RB1-HDAC1 complex, which negatively regulates the CREST-mediated transcription in resting neurons. Upon calcium stimulation, HDAC1 is released from the complex and CREBBP is recruited, which facilitates transcriptional activation. Deacetylates TSHZ3 and regulates its transcriptional repressor activity. Deacetylates 'Lys-310' in RELA and thereby inhibits the transcriptional activity of NF-kappa-B. Component a RCOR/GFI/KDM1A/HDAC complex that suppresses, via histone deacetylase (HDAC) recruitment, a number of genes implicated in multilineage blood cell development. Publication Abstract from PubMed MiDAC is one of seven distinct, large multi-protein complexes that recruit class I histone deacetylases to the genome to regulate gene expression. Despite implications of involvement in cell cycle regulation and in several cancers, surprisingly little is known about the function or structure of MiDAC. Here we show that MiDAC is important for chromosome alignment during mitosis in cancer cell lines. Mice lacking the MiDAC proteins, DNTTIP1 or MIDEAS, die with identical phenotypes during late embryogenesis due to perturbations in gene expression that result in heart malformation and haematopoietic failure. This suggests that MiDAC has an essential and unique function that cannot be compensated by other HDAC complexes. Consistent with this, the cryoEM structure of MiDAC reveals a unique and distinctive mode of assembly. Four copies of HDAC1 are positioned at the periphery with outward-facing active sites suggesting that the complex may target multiple nucleosomes implying a processive deacetylase function. The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure.,Turnbull RE, Fairall L, Saleh A, Kelsall E, Morris KL, Ragan TJ, Savva CG, Chandru A, Millard CJ, Makarova OV, Smith CJ, Roseman AM, Fry AM, Cowley SM, Schwabe JWR Nat Commun. 2020 Jun 26;11(1):3252. doi: 10.1038/s41467-020-17078-8. PMID:32591534 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone deacetylase 3D structures

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