6KBB

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

Summary for 6KBB

• Entry DOI: 10.2210/pdb6kbb/pdb
• Descriptor: Histone H2A type 1-D, Histone H2B type 2-E, SWR1-complex protein 5, ... (4 entities in total)
• Functional Keywords: histone chaperone, transcription
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 6
• Total formula weight: 62107.62

Authors

Huang, Y.,Zhou, Z. (deposition date: 2019-06-24, release date: 2020-01-29, Last modification date: 2023-11-22)

Primary citation

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.USA, 117:3543-3550, 2020

PubMed Abstract: 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-Å 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.

PubMed: 32001508
DOI: 10.1073/pnas.1914313117

Experimental method

X-RAY DIFFRACTION (2.365 Å)