title: Ubiquitin utilizes an acidic surface patch to alter chromatin structure.
abstract: Ubiquitylation of histone H2B, associated with gene activation, leads to chromatin decompaction through an unknown mechanism. We used a hydrogen-deuterium exchange strategy coupled with NMR spectroscopy to map the ubiquitin surface responsible for its structural effects on chromatin. Our studies revealed that a previously uncharacterized acidic patch on ubiquitin comprising residues Glu16 and Glu18 is essential for decompaction. These residues mediate promiscuous electrostatic interactions with the basic histone proteins, potentially positioning the ubiquitin moiety as a dynamic 'wedge' that prevents the intimate association of neighboring nucleosomes. Using two independent crosslinking strategies and an oligomerization assay, we also showed that ubiquitin-ubiquitin contacts occur in the chromatin environment and are important for the solubilization of the chromatin polymers. Our work highlights a novel, chromatin-related aspect of the 'ubiquitin code' and sheds light on how the information-rich ubiquitin modification can orchestrate different biochemical outcomes using distinct surface features.
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey, USA.
authors.forename: Galia T
authors.initials: GT
authors.lastname: Debelouchina
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey, USA.|Department of Chemistry, Technical University Munich, Garching, Germany.
authors.forename: Karola
authors.initials: K
authors.lastname: Gerecht
authors.affiliation: Department of Chemistry, Princeton University, Princeton, New Jersey, USA.
authors.forename: Tom W
authors.initials: TW
authors.lastname: Muir
mesh_terms: D002843:Chromatin / Q000737:chemistry* / Q000378:metabolism; D041961:Deuterium Exchange Measurement; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D055672:Static Electricity; D013499:Surface Properties; D025801:Ubiquitin / Q000737:chemistry / Q000378:metabolism*
chemical_list: D002843:Chromatin; D025801:Ubiquitin