title: Structure of full-length ubiquitin-conjugating enzyme E2-25K (huntingtin-interacting protein 2).
abstract: The ubiquitin-conjugating enzyme E2-25K has been identified as a huntingtin (the key protein in Huntington's disease) interacting protein and has been shown to play a role in mediating the toxicity of Abeta, the principal protein involved in Alzheimer's disease pathogenesis. E2-25K is a dual-domain protein with an ubiquitin-associated (UBA) domain as well as a conserved ubiquitin-conjugating (UBC) domain which catalyzes the formation of a covalent bond between the C-terminal glycine of an ubiquitin molecule and the -amine of a lysine residue on the acceptor protein as part of the ubiquitin-proteasome pathway. The crystal structures of E2-25K M172A mutant protein at pH 6.5 and pH 8.5 were determined to 1.9 and 2.2 A resolution, respectively. Examination of the structures revealed domain-domain interactions between the UBC and UBA domains which have not previously been reported.
authors.affiliation: University of Alabama in Huntsville, 35899, USA.
authors.forename: Randall C
authors.initials: RC
authors.lastname: Wilson
authors.forename: Ronny C
authors.initials: RC
authors.lastname: Hughes
authors.forename: Justin W
authors.initials: JW
authors.lastname: Flatt
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Meehan
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Ng
authors.forename: Pamela D
authors.initials: PD
authors.lastname: Twigg
mesh_terms: D002118:Calcium / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D017434:Protein Structure, Tertiary; D044763:Ubiquitin-Conjugating Enzymes / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D044763:Ubiquitin-Conjugating Enzymes; D002118:Calcium