8cok | pdb_00008cok
Structural analysis of ING3 protein and its binding to histone H3
Structural highlights
FunctionING3_RAT Component of the NuA4 histone acetyltransferase (HAT) complex which is involved in transcriptional activation of select genes principally by acetylation of nucleosomal histones H4 and H2A. This modification may both alter nucleosome - DNA interactions and promote interaction of the modified histones with other proteins which positively regulate transcription. This complex may be required for the activation of transcriptional programs associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest and replicative senescence, apoptosis, and DNA repair. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Component of a SWR1-like complex that specifically mediates the removal of histone H2A.Z/H2AZ1 from the nucleosome (By similarity). Publication Abstract from PubMedProteins belonging to the ING family regulate the transcriptional state of chromatin by recruiting remodeling complexes to sites with histone H3 trimethylated at Lysine 4 (H3K4me3). This modification is recognized by the Plant HomeoDomain (PHD) present at the C-terminal region of the five ING proteins. ING3 facilitates acetylation of histones H2A and H4 by the NuA4-Tip60 MYST histone acetyl transferase complex, and it has been proposed to be an oncoprotein. The crystal structure of the N-terminal domain of ING3 shows that it forms homodimers with an antiparallel coiled-coil fold. The crystal structure of the PHD is similar to those of its four homologs. These structures explain the possible deleterious effects of ING3 mutations detected in tumors. The PHD binds histone H3K4me3 with low-micromolar, and binds the non-methylated histone with a 54-fold reduced affinity. Our structure explains the impact of site directed mutagenesis experiments on histone recognition. These structural features could not be confirmed for the full-length protein as solubility was insufficient for structural studies, but the structure of its folded domains suggest a conserved structural organization for the ING proteins as homodimers and bivalent readers of the histone H3K4me3 mark. Structural analysis of ING3 protein and histone H3 binding.,Ferreras-Gutierrez M, Chaves-Arquero B, Gonzalez-Magana A, Merino N, Amusategui-Mateu I, Huecas S, Medrano FJ, Blanco FJ Int J Biol Macromol. 2023 May 4;242(Pt 1):124724. doi: , 10.1016/j.ijbiomac.2023.124724. PMID:37148949[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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