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

• Published in: Nucleic acids research 2016-07, Vol.44 (13), p.6157-6172
• Main Authors: Hammond, Colin M, Sundaramoorthy, Ramasubramanian, Larance, Mark, Lamond, Angus, Stevens, Michael A, El-Mkami, Hassane, Norman, David G, Owen-Hughes, Tom
• Format: Article
• Language: English
• Subjects: Acetylation; Cell Cycle Proteins - chemistry; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Crystallography, X-Ray; Gene regulation, Chromatin and Epigenetics; Histone Acetyltransferases - genetics; Histone Acetyltransferases - metabolism; Histone Chaperones - chemistry; Histone Chaperones - genetics; Histone Chaperones - metabolism; Histones - chemistry; Histones - genetics; Histones - metabolism; Molecular Chaperones - chemistry; Molecular Chaperones - genetics; Molecular Chaperones - metabolism; Multiprotein Complexes; Protein Binding; Protein Multimerization; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - chemistry; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism
• ISSN: 0305-1048; 1362-4962
• DOI: 10.1093/nar/gkw209

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.