title: Crystal structures of Lys-63-linked tri- and di-ubiquitin reveal a highly extended chain architecture.
abstract: The covalent attachment of different types of poly-ubiquitin chains signal different outcomes for the proteins so targeted. For example, a protein modified with Lys-48-linked poly-ubiquitin chains is targeted for proteasomal degradation, whereas Lys-63-linked chains encode nondegradative signals. The structural features that enable these different types of chains to encode different signals have not yet been fully elucidated. We report here the X-ray crystal structures of Lys-63-linked tri- and di-ubiquitin at resolutions of 2.3 and 1.9 A, respectively. The tri- and di-ubiquitin species adopt essentially identical structures. In both instances, the ubiquitin chain assumes a highly extended conformation with a left-handed helical twist; the helical chain contains four ubiquitin monomers per turn and has a repeat length of approximately 110 A. Interestingly, Lys-48 ubiquitin chains also adopt a left-handed helical structure with a similar repeat length. However, the Lys-63 architecture is much more open than that of Lys-48 chains and exposes much more of the ubiquitin surface for potential recognition events. These new crystal structures are consistent with the results of solution studies of Lys-63 chain conformation, and reveal the structural basis for differential recognition of Lys-63 versus Lys-48 chains.
authors.affiliation: Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, Pennsylvania 19102, USA.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Weeks
authors.forename: Kimberly C
authors.initials: KC
authors.lastname: Grasty
authors.forename: Lisa
authors.initials: L
authors.lastname: Hernandez-Cuebas
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Loll
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000737:chemistry; D008670:Metals / Q000378:metabolism; D008958:Models, Molecular; D025821:Polyubiquitin / Q000737:chemistry / Q000378:metabolism; D020836:Protein Structure, Quaternary; D011994:Recombinant Proteins / Q000378:metabolism; D044764:Ubiquitin-Activating Enzymes / Q000378:metabolism; D014452:Ubiquitins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008670:Metals; D011994:Recombinant Proteins; D014452:Ubiquitins; C075986:diubiquitin conjugate; D025821:Polyubiquitin; D044764:Ubiquitin-Activating Enzymes; D008239:Lysine