2lkm | pdb_00002lkm
Structural Basis for Molecular Interactions Involving MRG Domains: Implications in Chromatin Biology
Structural highlights
Function[PHF12_HUMAN] Acts as a transcriptional repressor. Involved in recruitment of functional SIN3A complexes to DNA. Represses transcription at least in part through the activity of an associated histone deacetylase (HDAC). May also repress transcription in a SIN3A-independent manner through recruitment of functional AES complexes to DNA.[1] [MO4L1_HUMAN] 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. The NuA4 complex ATPase and helicase activities seem to be, at least in part, contributed by the association of RUVBL1 and RUVBL2 with EP400. NuA4 may also play a direct role in DNA repair when directly recruited to sites of DNA damage. Also component of the mSin3A complex which acts to repress transcription by deacetylation of nucleosomal histones. Required for homologous recombination repair (HRR) and resistance to mitomycin C (MMC). Involved in the localization of PALB2, BRCA2 and RAD51, but not BRCA1, to DNA-damage foci.[2] [3] Publication Abstract from PubMedMRG15 is a member of the mortality family of transcription factors that targets a wide variety of multiprotein complexes involved in transcription regulation, DNA repair, and alternative splicing to chromatin. The structure of the apo-MRG15 MRG domain implicated in interactions with diverse proteins has been described, but not in complex with any of its targets. Here, we structurally and functionally characterize the interaction between MRG15 and Pf1, two constitutively associated subunits of the histone deacetylase-associated Rpd3S/Sin3S corepressor complex. The MRG domain adopts a structure reminiscent of the apo state, whereas the Pf1 MRG-binding domain engages two discrete hydrophobic surfaces on the MRG domain via a bipartite motif comprising an alpha-helix and a segment in an extended conformation, both of which are critical for high-affinity interactions. Multiple MRG15 interactors share an FxLP motif in the extended segment, but equivalent sequence/helical motifs are not readily evident, implying potential diversity in MRG-recognition mechanisms. Structural basis for molecular interactions involving MRG domains: implications in chromatin biology.,Xie T, Graveline R, Kumar GS, Zhang Y, Krishnan A, David G, Radhakrishnan I Structure. 2012 Jan 11;20(1):151-60. PMID:22244764[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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