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 Norman, Thomas Owen-Hughes (Lead / Corresponding author)

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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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Histone Chaperones
Histones
Electrons
Structural Models
X Ray Crystallography
Acetylation

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@article{155ddaff902e4f26b7cda20b8cef3ada,
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.",
author = "Hammond, {Colin M.} and Ramasubramanian Sundaramoorthy and Mark Larance and Angus Lamond and Stevens, {Michael A.} and Hassane El-Mkami and David Norman and Thomas Owen-Hughes",
note = "Wellcome Trust [094090, 097945, 099149]; Medical Research Council [G1100021]. Funding for open access charge: Wellcome Trust",
year = "2016",
month = "7",
day = "27",
doi = "10.1093/nar/gkw209",
language = "English",
volume = "44",
pages = "6157--6172",
journal = "Nucleic Acids Research",
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TY - JOUR

T1 - The histone chaperone Vps75 forms multiple oligomeric assemblies capable of mediating exchange between histone H3–H4 tetramers and Asf1–H3–H4 complexes

AU - Hammond, Colin M.

AU - Sundaramoorthy, Ramasubramanian

AU - Larance, Mark

AU - Lamond, Angus

AU - Stevens, Michael A.

AU - El-Mkami, Hassane

AU - Norman, David

AU - Owen-Hughes, Thomas

N1 - Wellcome Trust [094090, 097945, 099149]; Medical Research Council [G1100021]. Funding for open access charge: Wellcome Trust

PY - 2016/7/27

Y1 - 2016/7/27

N2 - 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.

AB - 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.

U2 - 10.1093/nar/gkw209

DO - 10.1093/nar/gkw209

M3 - Article

C2 - 27036862

VL - 44

SP - 6157

EP - 6172

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 13

ER -