TY - JOUR
T1 - Structural Basis for the Recognition of Methylated Histone H3K36 by the Eaf3 Subunit of Histone Deacetylase Complex Rpd3S
AU - Xu, Chao
AU - Cui, Gaofeng
AU - Botuyan, Maria Victoria
AU - Mer, Georges
N1 - Funding Information:
We thank Jerry Workman and Bing Li for helpful discussions, and Slobodan Macura, Nenad Juranic, and Prasanna Mishra at the Mayo Clinic NMR Core Facility for assistance. We are very grateful to Emeric Wasielewski for help with the figures. This work was supported by NIH grants CA109449 and CA132878 to G.M.
PY - 2008/11/12
Y1 - 2008/11/12
N2 - Deacetylation of nucleosomes by the Rpd3S histone deacetylase along the path of transcribing RNA polymerase II regulates access to DNA, contributing to faithful gene transcription. The association of Rpd3S with chromatin requires its Eaf3 subunit, which binds histone H3 methylated at lysine 36 (H3K36). Eaf3 is also part of NuA4 acetyltransferase that recognizes methylated H3K4. Here we show that Eaf3 in Saccharomyces cerevisiae contains a chromo barrel-related domain that binds methylated peptides, including H3K36 and H3K4, with low specificity and millimolar-range affinity. Nuclear magnetic resonance structure determination of Eaf3 bound to methylated H3K36 was accomplished by engineering a linked Eaf3-H3K36 molecule with a chemically incorporated methyllysine analog. Our study uncovers the molecular details of Eaf3-methylated H3K36 complex formation, and suggests that, in the cell, Eaf3 can only function within a framework of combinatorial interactions. This work also provides a general method for structure determination of low-affinity protein complexes implicated in methyllysine recognition.
AB - Deacetylation of nucleosomes by the Rpd3S histone deacetylase along the path of transcribing RNA polymerase II regulates access to DNA, contributing to faithful gene transcription. The association of Rpd3S with chromatin requires its Eaf3 subunit, which binds histone H3 methylated at lysine 36 (H3K36). Eaf3 is also part of NuA4 acetyltransferase that recognizes methylated H3K4. Here we show that Eaf3 in Saccharomyces cerevisiae contains a chromo barrel-related domain that binds methylated peptides, including H3K36 and H3K4, with low specificity and millimolar-range affinity. Nuclear magnetic resonance structure determination of Eaf3 bound to methylated H3K36 was accomplished by engineering a linked Eaf3-H3K36 molecule with a chemically incorporated methyllysine analog. Our study uncovers the molecular details of Eaf3-methylated H3K36 complex formation, and suggests that, in the cell, Eaf3 can only function within a framework of combinatorial interactions. This work also provides a general method for structure determination of low-affinity protein complexes implicated in methyllysine recognition.
KW - DNA
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U2 - 10.1016/j.str.2008.08.008
DO - 10.1016/j.str.2008.08.008
M3 - Article
C2 - 18818090
AN - SCOPUS:55249111484
SN - 0969-2126
VL - 16
SP - 1740
EP - 1750
JO - Structure
JF - Structure
IS - 11
ER -