Lys11-linked ubiquitin chains adopt compact conformations and are preferentially hydrolyzed by the deubiquitinase Cezanne.

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.
Mesh Terms:
Crystallography, X-Ray, Endopeptidases, Humans, Hydrolysis, Lysine, Magnetic Resonance Spectroscopy, Protein Structure, Quaternary, Protein Structure, Tertiary, Reproducibility of Results, Solutions, Substrate Specificity, Ubiquitin, Ubiquitin-Conjugating Enzymes, Ubiquitination
Nat. Struct. Mol. Biol.
Date: Aug. 01, 2010
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