title: Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne.
abstract: Ubiquitin is a versatile cellular signaling molecule that can form polymers of eight different linkages, and individual linkage types have been associated with distinct cellular functions. Though little is currently known about Lys11-linked ubiquitin chains, recent data indicate that they may be as abundant as Lys48 linkages and may be involved in vital cellular processes. Here we report the generation of Lys11-linked polyubiquitin in vitro, for which the Lys11-specific E2 enzyme UBE2S was fused to a ubiquitin binding domain. Crystallographic and NMR analyses of Lys11-linked diubiquitin reveal that Lys11-linked chains adopt compact conformations in which Ile44 is solvent exposed. Furthermore, we identify the OTU family deubiquitinase Cezanne as the first deubiquitinase with Lys11-linkage preference. Our data highlight the intrinsic specificity of the ubiquitin system that extends to Lys11-linked chains and emphasize that differentially linked polyubiquitin chains must be regarded as independent post-translational modifications.
authors.affiliation: Medical Research Council Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: Anja
authors.initials: A
authors.lastname: Bremm
authors.forename: Stefan M V
authors.initials: SM
authors.lastname: Freund
authors.forename: David
authors.initials: D
authors.lastname: Komander
mesh_terms: D018360:Crystallography, X-Ray; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008239:Lysine / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015203:Reproducibility of Results; D012996:Solutions; D013379:Substrate Specificity; D025801:Ubiquitin / Q000737:chemistry* / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry / Q000378:metabolism; D054875:Ubiquitination
chemical_list: D012996:Solutions; D025801:Ubiquitin; C544962:Ube2S protein, human; D044763:Ubiquitin-Conjugating Enzymes; D010450:Endopeptidases; C476458:OTUD7B protein, human; D008239:Lysine