Open AccessStructure of full‐length ubiquitin‐conjugating enzyme E2‐25K (huntingtin‐interacting protein 2)
Author(s) -
Wilson Randall C.,
Hughes Ronny C.,
Flatt Justin W.,
Meehan Edward J.,
Ng Joseph D.,
Twigg Pamela D.
Publication year - 2009
Publication title -
acta crystallographica section f
Language(s) - English
Resource type - Journals
ISSN - 1744-3091
DOI - 10.1107/s1744309109011117
Subject(s) - ubiquitin , deubiquitinating enzyme , ubiquitin conjugating enzyme , huntingtin , proteasome , lysine , chemistry , covalent bond , mutant , ubiquitin ligase , enzyme , biochemistry , protein structure , microbiology and biotechnology , biology , amino acid , gene , organic chemistry
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 Aβ, 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 ɛ‐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 Å resolution, respectively. Examination of the structures revealed domain–domain interactions between the UBC and UBA domains which have not previously been reported.