6kbb
From Proteopedia
Role of the DEF/Y motif of Swc5 in histone H2A.Z deposition
Structural highlights
Function[H2A1D_HUMAN] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [SWC5_YEAST] Component of the SWR1 complex which mediates the ATP-dependent exchange of histone H2A for the H2A variant HZT1 leading to transcriptional regulation of selected genes by chromatin remodeling. Involved in chromosome stability.[1] [2] [3] [H2B2E_HUMAN] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[4] [5] [6] Has broad antibacterial activity. May contribute to the formation of the functional antimicrobial barrier of the colonic epithelium, and to the bactericidal activity of amniotic fluid.[7] [8] [9] Publication Abstract from PubMedThe SWR complex edits the histone composition of nucleosomes at promoters to facilitate transcription by replacing the two nucleosomal H2A-H2B (A-B) dimers with H2A.Z-H2B (Z-B) dimers. Swc5, a subunit of SWR, binds to A-B dimers, but its role in the histone replacement reaction was unclear. In this study, we showed that Swc5 uses a tandem DEF/Y motif within an intrinsically disordered region to engage the A-B dimer. A 2.37-A X-ray crystal structure of the histone binding domain of Swc5 in complex with an A-B dimer showed that consecutive acidic residues and flanking hydrophobic residues of Swc5 form a cap over the histones, excluding histone-DNA interaction. Mutations in Swc5 DEF/Y inhibited the nucleosome editing function of SWR in vitro. Swc5 DEF/Y interacts with histones in vivo, and the extent of this interaction is dependent on the remodeling ATPase of SWR, supporting a model in which Swc5 acts as a wedge to promote A-B dimer eviction. Given that DEF/Y motifs are found in other evolutionary unrelated chromatin regulators, this work provides the molecular basis for a general strategy used repeatedly during eukaryotic evolution to mobilize histones in various genomic functions. Role of a DEF/Y motif in histone H2A-H2B recognition and nucleosome editing.,Huang Y, Sun L, Pierrakeas L, Dai L, Pan L, Luk E, Zhou Z Proc Natl Acad Sci U S A. 2020 Jan 30. pii: 1914313117. doi:, 10.1073/pnas.1914313117. PMID:32001508[10] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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