title: Structural basis for non-covalent interaction between ubiquitin and the ubiquitin conjugating enzyme variant human MMS2.
abstract: Modification of proteins by post-translational covalent attachment of a single, or chain, of ubiquitin molecules serves as a signaling mechanism for a number of regulatory functions in eukaryotic cells. For example, proteins tagged with lysine-63 linked polyubiquitin chains are involved in error-free DNA repair. The catalysis of lysine-63 linked polyubiquitin chains involves the sequential activity of three enzymes (E1, E2, and E3) that ultimately transfer a ubiquitin thiolester intermediate to a protein target. The E2 responsible for catalysis of lysine-63 linked polyubiquitination is a protein heterodimer consisting of a canonical E2 known as Ubc13, and an E2-like protein, or ubiquitin conjugating enzyme variant (UEV), known as Mms2. We have determined the solution structure of the complex formed by human Mms2 and ubiquitin using high resolution, solution state nuclear magnetic resonance (NMR) spectroscopy. The structure of the Mms2-Ub complex provides important insights into the molecular basis underlying the catalysis of lysine-63 linked polyubiquitin chains.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lewis
authors.forename: Linda F
authors.initials: LF
authors.lastname: Saltibus
authors.forename: D Duong
authors.initials: DD
authors.lastname: Hau
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
authors.forename: Leo
authors.initials: L
authors.lastname: Spyracopoulos
mesh_terms: D006801:Humans; D008025:Ligases / Q000737:chemistry*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D025801:Ubiquitin / Q000737:chemistry*; D044763:Ubiquitin-Conjugating Enzymes
chemical_list: D025801:Ubiquitin; C114715:UBE2V2 protein, human; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases