Abstract
The histone chaperone Vps75 presents the remarkable property of stimulating the Rtt109-dependent acetylation of several histone H3 lysine residues within (H3-H4)(2) tetramers. To investigate this activation mechanism, we determined x-ray structures of full-length Vps75 in complex with full-length Rtt109 in two crystal forms. Both structures show similar asymmetric assemblies of a Vps75 dimer bound to an Rtt109 monomer. In the Vps75-Rtt109 complexes, the catalytic site of Rtt109 is confined to an enclosed space that can accommodate the N-terminal tail of histone H3 in (H3-H4)(2). Investigation of Vps75-Rtt109-(H3-H4)(2) and Vps75-(H3-H4)(2) complexes by NMR spectroscopy-probed hydrogen/deuterium exchange suggests that Vps75 guides histone H3 in the catalytic enclosure. These findings clarify the basis for the enhanced acetylation of histone H3 tail residues by Vps75-Rtt109.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acetylation
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Crystallography, X-Ray
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Histone Acetyltransferases / chemistry*
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Histone Acetyltransferases / genetics
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Histone Acetyltransferases / metabolism
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Histones / chemistry*
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Histones / genetics
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Histones / metabolism
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Molecular Chaperones / chemistry*
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Molecular Chaperones / genetics
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Molecular Chaperones / metabolism
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Multiprotein Complexes / chemistry*
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Multiprotein Complexes / genetics
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Multiprotein Complexes / metabolism
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Protein Multimerization
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Protein Structure, Quaternary
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Protein Structure, Tertiary
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Saccharomyces cerevisiae / chemistry*
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins / chemistry*
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / metabolism
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Structure-Activity Relationship
Substances
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Histones
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Molecular Chaperones
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Multiprotein Complexes
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Saccharomyces cerevisiae Proteins
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Vps75 protein, S cerevisiae
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Histone Acetyltransferases
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Rtt109 protein, S cerevisiae