title: The Role of Electrostatic Interactions in Binding of Histone H3K4me2/3 to the Sgf29 Tandem Tudor Domain.
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.
authors.affiliation: Institute of Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Bas J G E
authors.initials: BJ
authors.lastname: Pieters
authors.affiliation: Institute of Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Meulenbroeks
authors.affiliation: Institute of Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Roman
authors.initials: R
authors.lastname: Belle
authors.affiliation: Institute of Molecules and Materials, Radboud University Nijmegen, Nijmegen, The Netherlands.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Mecinović
mesh_terms: D000123:Acetyltransferases / Q000737:chemistry* / Q000378:metabolism*; D001224:Aspartic Acid / Q000378:metabolism; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D008958:Models, Molecular; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D006657:Histones; D001224:Aspartic Acid; D000123:Acetyltransferases; D008239:Lysine