1YLA

Ubiquitin-conjugating enzyme E2-25 kDa (Huntington interacting protein 2)

Summary for 1YLA

• Entry DOI: 10.2210/pdb1yla/pdb
• Descriptor: Ubiquitin-conjugating enzyme E2-25 kDa (2 entities in total)
• Functional Keywords: ubiquitin, ubiquitin- conjugating enzyme, ligase, structural genomics, sgc, structural genomics consortium
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm (By similarity): P61086
• Total number of polymer chains: 2
• Total formula weight: 45149.44

Authors

Choe, J.,Avvakumov, G.V.,Newman, E.M.,Mackenzie, F.,Kozieradzki, I.,Bochkarev, A.,Sundstrom, M.,Arrowsmith, C.,Edwards, A.,Dhe-paganon, S.,Structural Genomics Consortium (SGC) (deposition date: 2005-01-19, release date: 2005-02-01, Last modification date: 2023-08-23)

Primary citation

Ko, S.,Kang, G.B.,Song, S.M.,Lee, J.-G.,Shin, D.Y.,Yun, J.-H.,Sheng, Y.,Cheong, C.,Jeon, Y.H.,Jung, Y.-K.,Arrowsmith, C.H.,Avvakumov, G.V.,Dhe-Paganon, S.,Yoo, Y.J.,Eom, S.H.,Lee, W.
Structural basis of E2-25K/UBB+1 interaction leading to proteasome inhibition and neurotoxicity
J.Biol.Chem., 285:36070-36080, 2010

PubMed Abstract: 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-β 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 α9 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.

PubMed: 20826778
DOI: 10.1074/jbc.M110.145219

Experimental method

X-RAY DIFFRACTION (2.4 Å)