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The Role of Electrostatic Interactions in Binding of Histone H3K4me2/3 to the Sgf29 Tandem Tudor Domain.

Pieters BJ, Meulenbroeks E, Belle R, Mecinović J - PLoS ONE (2015)

Bottom Line: Several reader domain proteins that specifically recognize methyllysine-containing histones contain the negatively-charged aspartate or glutamate residues as part of the aromatic cage.Small uncharged and large aromatic substitutions on the Asp266 site resulted in a significant decrease in binding affinities for both H3K4me3 and H3K4me2, demonstrating the role of the negative charge of Asp266 in the readout process by Sgf29.This study emphasizes the essential contribution of electrostatic interactions to the overall binding affinity, and reveals that the underlying mechanisms for the recognition of Kme2/3 depend on the composition and arrangement of the aromatic cage.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands.

ABSTRACT
Several reader domain proteins that specifically recognize methyllysine-containing histones contain the negatively-charged aspartate or glutamate residues as part of the aromatic cage. Herein, we report thermodynamic analyses for the recognition of histone H3K4me3 and H3K4me2 by the tandem tudor domain of Sgf29 and its recognition site variants. Small uncharged and large aromatic substitutions on the Asp266 site resulted in a significant decrease in binding affinities for both H3K4me3 and H3K4me2, demonstrating the role of the negative charge of Asp266 in the readout process by Sgf29. This study emphasizes the essential contribution of electrostatic interactions to the overall binding affinity, and reveals that the underlying mechanisms for the recognition of Kme2/3 depend on the composition and arrangement of the aromatic cage.

No MeSH data available.


Crystal structure of Sgf29-H3K4me3 (A, PDB ID: 3ME9), Sgf29-H3K4me2 (B, PDB ID: 3MET) and the apo form of Sgf29 (C, PDB ID: 3MEW).Sgf29 and H3K4me2/3 histone peptide are shown in cyan and yellow, respectively.
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pone.0139205.g001: Crystal structure of Sgf29-H3K4me3 (A, PDB ID: 3ME9), Sgf29-H3K4me2 (B, PDB ID: 3MET) and the apo form of Sgf29 (C, PDB ID: 3MEW).Sgf29 and H3K4me2/3 histone peptide are shown in cyan and yellow, respectively.

Mentions: Sgf29 (SAGA-associated Factor 29) is a subunit of the SAGA (Spt-Ada-Gcn5 acetyltransferase) complex, a chromatin modifying complex, which is capable of acetylating and deubiquitinating histone proteins.[9,10]. Crystallographic work has shown that Sgf29 contains a tandem tudor domain with each tudor domain having a negatively-charged pocket capable of binding H3A1 and an aromatic cage for the recognition of H3K4me2/3 residues (Fig 1).[11]. The aromatic cage is composed of 3 aromatic amino acid residues and a negatively-charged aspartate (Y238, Y245, F264, and D266), with F264 being positioned at the edge of the recognition site. Thermodynamic analyses have confirmed the requirement of the H3A1 recognition site for adequate binding of H3K4me3 peptides to Sgf29 and that only the first four N-terminal amino acid residues (ARTKme3) are essentially required for binding of H3K4me3 peptides to the Sgf29 reader domain[12].


The Role of Electrostatic Interactions in Binding of Histone H3K4me2/3 to the Sgf29 Tandem Tudor Domain.

Pieters BJ, Meulenbroeks E, Belle R, Mecinović J - PLoS ONE (2015)

Crystal structure of Sgf29-H3K4me3 (A, PDB ID: 3ME9), Sgf29-H3K4me2 (B, PDB ID: 3MET) and the apo form of Sgf29 (C, PDB ID: 3MEW).Sgf29 and H3K4me2/3 histone peptide are shown in cyan and yellow, respectively.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4589357&req=5

pone.0139205.g001: Crystal structure of Sgf29-H3K4me3 (A, PDB ID: 3ME9), Sgf29-H3K4me2 (B, PDB ID: 3MET) and the apo form of Sgf29 (C, PDB ID: 3MEW).Sgf29 and H3K4me2/3 histone peptide are shown in cyan and yellow, respectively.
Mentions: Sgf29 (SAGA-associated Factor 29) is a subunit of the SAGA (Spt-Ada-Gcn5 acetyltransferase) complex, a chromatin modifying complex, which is capable of acetylating and deubiquitinating histone proteins.[9,10]. Crystallographic work has shown that Sgf29 contains a tandem tudor domain with each tudor domain having a negatively-charged pocket capable of binding H3A1 and an aromatic cage for the recognition of H3K4me2/3 residues (Fig 1).[11]. The aromatic cage is composed of 3 aromatic amino acid residues and a negatively-charged aspartate (Y238, Y245, F264, and D266), with F264 being positioned at the edge of the recognition site. Thermodynamic analyses have confirmed the requirement of the H3A1 recognition site for adequate binding of H3K4me3 peptides to Sgf29 and that only the first four N-terminal amino acid residues (ARTKme3) are essentially required for binding of H3K4me3 peptides to the Sgf29 reader domain[12].

Bottom Line: Several reader domain proteins that specifically recognize methyllysine-containing histones contain the negatively-charged aspartate or glutamate residues as part of the aromatic cage.Small uncharged and large aromatic substitutions on the Asp266 site resulted in a significant decrease in binding affinities for both H3K4me3 and H3K4me2, demonstrating the role of the negative charge of Asp266 in the readout process by Sgf29.This study emphasizes the essential contribution of electrostatic interactions to the overall binding affinity, and reveals that the underlying mechanisms for the recognition of Kme2/3 depend on the composition and arrangement of the aromatic cage.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands.

ABSTRACT
Several reader domain proteins that specifically recognize methyllysine-containing histones contain the negatively-charged aspartate or glutamate residues as part of the aromatic cage. Herein, we report thermodynamic analyses for the recognition of histone H3K4me3 and H3K4me2 by the tandem tudor domain of Sgf29 and its recognition site variants. Small uncharged and large aromatic substitutions on the Asp266 site resulted in a significant decrease in binding affinities for both H3K4me3 and H3K4me2, demonstrating the role of the negative charge of Asp266 in the readout process by Sgf29. This study emphasizes the essential contribution of electrostatic interactions to the overall binding affinity, and reveals that the underlying mechanisms for the recognition of Kme2/3 depend on the composition and arrangement of the aromatic cage.

No MeSH data available.