The histone chaperone Vps75 forms multiple oligomeric assemblies capable of mediating exchange between histone H3-H4 tetramers and Asf1-H3-H4 complexes

Colin M. Hammond, Ramasubramanian Sundaramoorthy, Mark Larance, Angus Lamond, Michael A. Stevens, Hassane El-Mkami, David G. Norman, Tom Owen-Hughes*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)
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Abstract

Vps75 is a histone chaperone that has been historically characterized as homodimer by X-ray crystallography. In this study, we present a crystal structure containing two related tetrameric forms of Vps75 within the crystal lattice. We show Vps75 associates with histones in multiple oligomers. In the presence of equimolar H3-H4 and Vps75, the major species is a reconfigured Vps75 tetramer bound to a histone H3-H4 tetramer. However, in the presence of excess histones, a Vps75 dimer bound to a histone H3-H4 tetramer predominates. We show the Vps75-H3-H4 interaction is compatible with the histone chaperone Asf1 and deduce a structural model of the Vps75-Asf1-H3-H4 (VAH) co-chaperone complex using the Pulsed Electron-electron Double Resonance (PELDOR) technique and cross-linking MS/MS distance restraints. The model provides a molecular basis for the involvement of both Vps75 and Asf1 in Rtt109 catalysed histone H3 K9 acetylation. In the absence of Asf1 this model can be used to generate a complex consisting of a reconfigured Vps75 tetramer bound to a H3-H4 tetramer. This provides a structural explanation for many of the complexes detected biochemically and illustrates the ability of Vps75 to interact with dimeric or tetrameric H3-H4 using the same interaction surface.

Original languageEnglish
Pages (from-to)6157-6172
Number of pages16
JournalNucleic Acids Research
Volume44
Issue number13
Early online date1 Apr 2016
DOIs
Publication statusPublished - 27 Jul 2016

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