title: The histone chaperone Vps75 forms multiple oligomeric assemblies capable of mediating exchange between histone H3-H4 tetramers and Asf1-H3-H4 complexes.
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.
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Colin M
authors.initials: CM
authors.lastname: Hammond
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Ramasubramanian
authors.initials: R
authors.lastname: Sundaramoorthy
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Larance
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Angus
authors.initials: A
authors.lastname: Lamond
authors.affiliation: Nucleic Acids Structure Research Group, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Stevens
authors.affiliation: School of Physics and Astronomy, University of St Andrews, St Andrews, KY16 9SS, UK.
authors.forename: Hassane
authors.initials: H
authors.lastname: El-Mkami
authors.affiliation: Nucleic Acids Structure Research Group, University of Dundee, Dundee DD1 5EH, UK.
authors.forename: David G
authors.initials: DG
authors.lastname: Norman
authors.affiliation: Centre for Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee DD1 5EH, UK t.a.owenhughes@dundee.ac.uk.
authors.forename: Tom
authors.initials: T
authors.lastname: Owen-Hughes
mesh_terms: D000107:Acetylation; D018797:Cell Cycle Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism; D056488:Histone Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018832:Molecular Chaperones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D046912:Multiprotein Complexes; D011485:Protein Binding; D055503:Protein Multimerization; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D056488:Histone Chaperones; D006657:Histones; D018832:Molecular Chaperones; D046912:Multiprotein Complexes; D029701:Saccharomyces cerevisiae Proteins; C525548:Vps75 protein, S cerevisiae; D051548:Histone Acetyltransferases