4afl
From Proteopedia
The crystal structure of the ING4 dimerization domain reveals the functional organization of the ING family of chromatin binding proteins.
Structural highlights
Function[ING4_HUMAN] Component of the HBO1 complex which has a histone H4-specific acetyltransferase activity, a reduced activity toward histone H3 and is responsible for the bulk of histone H4 acetylation in vivo. Through chromatin acetylation it may function in DNA replication. May inhibit tumor progression by modulating the transcriptional output of signaling pathways which regulate cell proliferation. Can suppress brain tumor angiogenesis through transcriptional repression of RELA/NFKB3 target genes when complexed with RELA. May also specifically suppress loss of contact inhibition elicited by activated oncogenes such as MYC. Represses hypoxia inducible factor's (HIF) activity by interacting with HIF prolyl hydroxylase 2 (EGLN1).[1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe protein ING4 binds to histone H3 trimethylated at Lys4 (H3K4me3) through its C-terminal PlantHomeoDomain (PHD), thus recruiting the HBO1 histone acetyltransferase complex to target promoters. The structure of the PHD finger bound to an H3K4me3 peptide has been described, as well as the disorder and flexibility in the ING4 central region. We report the crystal structure of the ING4 N-terminal domain, which shows an antiparallel coiled-coil homodimer with each protomer folded into a helix-loop-helix structure. This arrangement suggests that ING4 can bind simultaneously two histone tails, on the same or different nucleosomes. Dimerization has a direct impact on ING4 tumor suppressor activity since monomeric mutants lose the ability of inducing apoptosis after genotoxic stress. Homology modeling based on the ING4 structure suggests that other ING dimers may also exist. The crystal structure of the inhibitor of growth 4 (ING4) dimerization domain reveals the functional organization of the ING family of chromatin binding proteins.,Culurgioni S, Munoz IG, Moreno A, Palacios A, Villate M, Palmero I, Montoya G, Blanco FJ J Biol Chem. 2012 Feb 9. PMID:22334692[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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