Title | Ubiquitin utilizes an acidic surface patch to alter chromatin structure. |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Debelouchina, GT, Gerecht, K, Muir, TW |
Journal | Nat Chem Biol |
Volume | 13 |
Issue | 1 |
Pagination | 105-110 |
Date Published | 2017 Jan |
ISSN | 1552-4469 |
Keywords | Chromatin, Deuterium Exchange Measurement, Humans, Magnetic Resonance Spectroscopy, Models, Molecular, Static Electricity, Surface Properties, Ubiquitin |
Abstract | <p>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.</p> |
DOI | 10.1038/nchembio.2235 |
Alternate Journal | Nat Chem Biol |
PubMed ID | 27870837 |
PubMed Central ID | PMC5161692 |
Grant List | P01 CA196539 / CA / NCI NIH HHS / United States R01 GM107047 / GM / NIGMS NIH HHS / United States R37 GM086868 / GM / NIGMS NIH HHS / United States |