title: Structural Basis for Multi-specificity of MRG Domains.
abstract: Chromatin-binding proteins play vital roles in the assembly and recruitment of multi-subunit complexes harboring effector proteins to specific genomic loci. MRG15, a chromodomain-containing chromatin-binding protein, recruits diverse chromatin-associated complexes that regulate gene transcription, DNA repair, and RNA splicing. Previous studies with Pf1, another chromatin-binding subunit of the Sin3S/Rpd3S histone deacetylase complex, defined the sequence and structural requirements for interactions with the MRG15 MRG domain, a common target of diverse subunits in the aforementioned complexes. We now show that MRGBP, a member of the Tip60/NuA4 histone acetyltransferase complex, engages the same two surfaces of the MRG domain as Pf1. High-affinity interactions occur via a bipartite structural motif including an FxLP sequence motif. MRGBP shares little sequence and structural similarity with Pf1, yet targets similar pockets on the surface of the MRG domain, mimicking Pf1 in its interactions. Our studies shed light onto how MRG domains have evolved to bind diverse targets.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Xie
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Adam M
authors.initials: AM
authors.lastname: Zmyslowski
authors.affiliation: Department of Chemistry, Northwestern University, Evanston, IL 60208, USA.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA. Electronic address: i-radhakrishnan@northwestern.edu.
authors.forename: Ishwar
authors.initials: I
authors.lastname: Radhakrishnan
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000235:genetics; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D019143:Evolution, Molecular; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000235:genetics*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000235:genetics; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C470833:MORF4L1 protein, human; C479739:MRGBP protein, human; D046912:Multiprotein Complexes; D009687:Nuclear Proteins; D014157:Transcription Factors; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases