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1yla
From Proteopedia
| 1yla, resolution 2.40Å () | |||||||||
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| Gene: | HIP2, LIG (Homo sapiens) | ||||||||
| Activity: | Ubiquitin--protein ligase, with EC number 6.3.2.19 | ||||||||
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||
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 complexes. The structures revealed that ubiquitin or UBB+1 is bound to E2-25K via the enzyme's MGF motif and residues in alpha 9 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 polyUb. These results suggest that the interaction between E2-25K and UBB+1 is critical for the synthesis and accumulation of UBB+1-anchored polyUb, which results in proteasomal inhibition and neuronal cell death.
Structural basis of E2-25K/UBB+1 interaction leading to proteasome inhibition and neurotoxicity., Ko S, Kang GB, Song SM, Lee JG, Shin DY, Yoon J, Sheng Y, Cheong C, Jeon YH, Jung YK, Arrowsmith CH, Avvakumov GV, Dhe-Paganon S, Yoo YJ, Eom SH, Lee W, J Biol Chem. 2010 Sep 8. PMID:20826778
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
About this Structure
1YLA is a 2 chains structure with sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
- Ko S, Kang GB, Song SM, Lee JG, Shin DY, Yoon J, Sheng Y, Cheong C, Jeon YH, Jung YK, Arrowsmith CH, Avvakumov GV, Dhe-Paganon S, Yoo YJ, Eom SH, Lee W. Structural basis of E2-25K/UBB+1 interaction leading to proteasome inhibition and neurotoxicity. J Biol Chem. 2010 Sep 8. PMID:20826778 doi:10.1074/jbc.M110.145219
Page seeded by OCA on Thu Nov 18 00:20:04 2010
Categories: Homo sapiens | Ubiquitin--protein ligase | Arrowsmith, C. | Avvakumov, G V. | Bochkarev, A. | Choe, J. | Dhe-paganon, S. | Edwards, A. | Kozieradzki, I. | Mackenzie, F. | Newman, E M. | SGC, Structural Genomics Consortium. | Sundstrom, M. | Ligase | Sgc | Structural genomic | Structural genomics consortium | Ubiquitin | Ubiquitin- conjugating enzyme
