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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 20 151-60 (2012)
Cited: 19 times
EuropePMC logo PMID: 22244764

Abstract

MRG15 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 α-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.

Articles - 2lkm mentioned but not cited (6)

  1. Nucleosome contact triggers conformational changes of Rpd3S driving high-affinity H3K36me nucleosome engagement. Ruan C, Lee CH, Cui H, Li S, Li B. Cell Rep 10 204-215 (2015)
  2. 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 20 151-160 (2012)
  3. Structural Basis for Multi-specificity of MRG Domains. Xie T, Zmyslowski AM, Zhang Y, Radhakrishnan I. Structure 23 1049-1057 (2015)
  4. Homodimeric PHD Domain-containing Rco1 Subunit Constitutes a Critical Interaction Hub within the Rpd3S Histone Deacetylase Complex. Ruan C, Cui H, Lee CH, Li S, Li B. J Biol Chem 291 5428-5438 (2016)
  5. Structural basis of nucleosome deacetylation and DNA linker tightening by Rpd3S histone deacetylase complex. Dong S, Li H, Wang M, Rasheed N, Zou B, Gao X, Guan J, Li W, Zhang J, Wang C, Zhou N, Shi X, Li M, Zhou M, Huang J, Li H, Zhang Y, Wong KH, Zhang X, Chao WCH, He J. Cell Res 33 790-801 (2023)
  6. Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex. Wan MSM, Muhammad R, Koliopoulos MG, Roumeliotis TI, Choudhary JS, Alfieri C. Nat Commun 14 2556 (2023)


Reviews citing this publication (2)

  1. PALB2: the hub of a network of tumor suppressors involved in DNA damage responses. Park JY, Zhang F, Andreassen PR. Biochim Biophys Acta 1846 263-275 (2014)
  2. Structural and functional insights into the epigenetic regulator MRG15. Jiang N, Li YB, Jin JY, Guo JY, Ding QR, Meng D, Zhi XL. Acta Pharmacol Sin (2024)

Articles citing this publication (11)

  1. Characterization of native protein complexes and protein isoform variation using size-fractionation-based quantitative proteomics. Kirkwood KJ, Ahmad Y, Larance M, Lamond AI. Mol Cell Proteomics 12 3851-3873 (2013)
  2. Maintenance of interphase chromosome compaction and homolog pairing in Drosophila is regulated by the condensin cap-h2 and its partner Mrg15. Smith HF, Roberts MA, Nguyen HQ, Peterson M, Hartl TA, Wang XJ, Klebba JE, Rogers GC, Bosco G. Genetics 195 127-146 (2013)
  3. Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila. Huang C, Yang F, Zhang Z, Zhang J, Cai G, Li L, Zheng Y, Chen S, Xi R, Zhu B. Nat Commun 8 1649 (2017)
  4. MYC Mediates mRNA Cap Methylation of Canonical Wnt/β-Catenin Signaling Transcripts By Recruiting CDK7 and RNA Methyltransferase. Posternak V, Ung MH, Cheng C, Cole MD. Mol Cancer Res 15 213-224 (2017)
  5. Regulation and function of H3K36 di-methylation by the trithorax-group protein complex AMC. Schmähling S, Meiler A, Lee Y, Mohammed A, Finkl K, Tauscher K, Israel L, Wirth M, Philippou-Massier J, Blum H, Habermann B, Imhof A, Song JJ, Müller J. Development 145 dev163808 (2018)
  6. Sequence requirements for combinatorial recognition of histone H3 by the MRG15 and Pf1 subunits of the Rpd3S/Sin3S corepressor complex. Kumar GS, Chang W, Xie T, Patel A, Zhang Y, Wang GG, David G, Radhakrishnan I. J Mol Biol 422 519-531 (2012)
  7. PALB2 (partner and localizer of BRCA2). Hanenberg H, Andreassen PR. Atlas Genet Cytogenet Oncol Haematol 22 484-490 (2018)
  8. Condensin II Regulates Interphase Chromatin Organization Through the Mrg-Binding Motif of Cap-H2. Wallace HA, Klebba JE, Kusch T, Rogers GC, Bosco G. G3 (Bethesda) 5 803-817 (2015)
  9. The Chromatin-Associated Phf12 Protein Maintains Nucleolar Integrity and Prevents Premature Cellular Senescence. Graveline R, Marcinkiewicz K, Choi S, Paquet M, Wurst W, Floss T, David G. Mol Cell Biol 37 e00522-16 (2017)
  10. SIN-3 acts in distinct complexes to regulate the germline transcriptional program in Caenorhabditis elegans. Robert VJ, Caron M, Gely L, Adrait A, Pakulska V, Couté Y, Chevalier M, Riedel CG, Bedet C, Palladino F. Development 150 dev201755 (2023)
  11. Structural Insight into the Mechanism of PALB2 Interaction with MRG15. Redington J, Deveryshetty J, Kanikkannan L, Miller I, Korolev S. Genes (Basel) 12 2002 (2021)


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