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PMID: 17166288 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, U.S. Gov't, Non-P.H.S.

Structure of the yeast histone H3-ASF1 interaction: implications for chaperone mechanism, species-specific interactions, and epigenetics.

BMC structural biology ·Vol. 6 ·2006-12-13 ·Pages 26

Antczak AJ, Tsubota T, Kaufman PD, Berger JM

Abstract

The histone H3/H4 chaperone Asf1 (anti-silencing function 1) is required for the establishment and maintenance of proper chromatin structure, as well as for genome stability in eukaryotes. Asf1 participates in both DNA replication-coupled (RC) and replication-independent (RI) histone deposition reactions in vitro and interacts with complexes responsible for both pathways in vivo. Asf1 is known to directly bind histone H3, however, high-resolution structural information about the geometry of this interaction was previously unknown. Here we report the structure of a histone/histone chaperone interaction. We have solved the 2.2 A crystal structure of the conserved N-terminal immunoglobulin fold domain of yeast Asf1 (residues 2-155) bound to the C-terminal helix of yeast histone H3 (residues 121-134). The structure defines a histone-binding patch on Asf1 consisting of both conserved and yeast-specific residues; mutation of these residues abrogates H3/H4 binding affinity. The geometry of the interaction indicates that Asf1 binds to histones H3/H4 in a manner that likely blocks sterically the H3/H3 interface of the nucleosomal four-helix bundle. These data clarify how Asf1 regulates histone stoichiometry to modulate epigenetic inheritance. The structure further suggests a physical model in which Asf1 contributes to interpretation of a "histone H3 barcode" for sorting H3 isoforms into different deposition pathways.

MeSH Terms
Animals Cell Cycle Proteins/chemistry,genetics Dimerization Epigenesis, Genetic Gene Silencing Humans Molecular Chaperones/chemistry,genetics Protein Binding Saccharomyces cerevisiae/chemistry,genetics Silent Information Regulator Proteins, Saccharomyces cerevisiae/chemistry,genetics Species Specificity
Chemicals
ASF1A protein, human Cell Cycle Proteins Molecular Chaperones Silent Information Regulator Proteins, Saccharomyces cerevisiae
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Antczak Andrew J
Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA. antczaka@berkeley.edu <antczaka@berkeley.edu>
Tsubota Toshiaki
Kaufman Paul D
Berger James M
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Article Info
Journal
BMC structural biology
Abbr.
BMC Struct Biol
ISSN
1472-6807
Published
2006-12-13
Epub
2006-00-13
Pages
26
Language
English
Region
England
NLM ID
101088689
PMCID
PMC1762009
Subset
IM
Grants
NCI NIH HHS · R01 CA077373 · United States
NCI NIH HHS · CA077373 · United States
Databases
PDB
Analysis Services
Analysis Services

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