6kbb

From Proteopedia

Role of the DEF/Y motif of Swc5 in histone H2A.Z deposition

PDB ID 6kbb

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Structural highlights

6kbb is a 6 chain structure with sequence from Homo sapiens and Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.365Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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.

Publication Abstract from PubMed

The 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^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Huang Y, Sun L, Pierrakeas L, Dai L, Pan L, Luk E, Zhou Z. Role of a DEF/Y motif in histone H2A-H2B recognition and nucleosome editing. Proc Natl Acad Sci U S A. 2020 Jan 30. pii: 1914313117. doi:, 10.1073/pnas.1914313117. PMID:32001508 doi:http://dx.doi.org/10.1073/pnas.1914313117