1YLA: Ubiquitin-Conjugating Enzyme E2-25 Kda (Huntington Interacting Protein 2)

E2-25K/Hip2 is an unusual ubiquitin-conjugating enzyme that interacts with the frameshift mutant of ubiquitin B (UBB(+1)) and has been identified as a crucial factor regulating amyloid-beta neurotoxicity. To study the structural basis of the neurotoxicity mediated by the E2-25K-UBB(+1) interaction, we determined the three-dimensional structures of UBB(+1), E2-25K and the E2-25K/ubiquitin, and E2-25K/UBB(+1) complex. The structures revealed that ubiquitin or UBB(+1) is bound to E2-25K via the enzyme MGF motif and residues in alpha9 of the enzyme. Polyubiquitylation assays together with analyses of various E2-25K mutants showed that disrupting UBB(+1) binding markedly diminishes synthesis of neurotoxic UBB(+1)-anchored polyubiquitin. These results suggest that the interaction between E2-25K and UBB(+1) is critical for the synthesis and accumulation of UBB(+1)-anchored polyubiquitin, which results in proteasomal inhibition and neuronal cell death.
PDB ID: 1YLADownload
MMDB ID: 31574
PDB Deposition Date: 2005/1/19
Updated in MMDB: 2006/12
Experimental Method:
x-ray diffraction
Resolution: 2.4  Å
Source Organism:
Similar Structures:
Biological Unit for 1YLA: dimeric; determined by author
Molecular Components in 1YLA
Label Count Molecule
Proteins (2 molecules)
Ubiquitin-conjugating Enzyme E2-25 KDA(Gene symbol: UBE2K)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB