title: Structural basis for molecular interactions involving MRG domains: implications in chromatin biology.
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.
authors.affiliation: Department of Molecular Biosciences, Northwestern University, 2205 Tech Drive, Evanston, IL 60208, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Xie
authors.forename: Richard
authors.initials: R
authors.lastname: Graveline
authors.forename: Ganesan Senthil
authors.initials: GS
authors.lastname: Kumar
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Arvind
authors.initials: A
authors.lastname: Krishnan
authors.forename: Gregory
authors.initials: G
authors.lastname: David
authors.forename: Ishwar
authors.initials: I
authors.lastname: Radhakrishnan
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D002843:Chromatin / Q000378:metabolism*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D056264:Sin3 Histone Deacetylase and Corepressor Complex / Q000737:chemistry* / Q000378:metabolism*; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002843:Chromatin; C470833:MORF4L1 protein, human; D014157:Transcription Factors; D056264:Sin3 Histone Deacetylase and Corepressor Complex