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Title | Structure of the Cdc48 ATPase with its ubiquitin-binding cofactor Ufd1-Npl4. |
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Journal, issue, pages | Nat Struct Mol Biol, Vol. 25, Issue 7, Page 616-622, Year 2018 |
Publish date | Jul 2, 2018 |
Authors | Nicholas O Bodnar / Kelly H Kim / Zhejian Ji / Thomas E Wales / Vladimir Svetlov / Evgeny Nudler / John R Engen / Thomas Walz / Tom A Rapoport / |
PubMed Abstract | Many polyubiquitinated proteins are extracted from membranes or complexes by the conserved ATPase Cdc48 (in yeast; p97 or VCP in mammals) before proteasomal degradation. Each Cdc48 hexamer contains ...Many polyubiquitinated proteins are extracted from membranes or complexes by the conserved ATPase Cdc48 (in yeast; p97 or VCP in mammals) before proteasomal degradation. Each Cdc48 hexamer contains two stacked ATPase rings (D1 and D2) and six N-terminal (N) domains. Cdc48 binds various cofactors, including the Ufd1-Npl4 heterodimer. Here, we report structures of the Cdc48-Ufd1-Npl4 complex from Chaetomium thermophilum. Npl4 interacts through its UBX-like domain with a Cdc48 N domain, and it uses two Zn-finger domains to anchor the enzymatically inactive Mpr1-Pad1 N-terminal (MPN) domain, homologous to domains found in several isopeptidases, to the top of the D1 ATPase ring. The MPN domain of Npl4 is located above Cdc48's central pore, a position similar to the MPN domain from deubiquitinase Rpn11 in the proteasome. Our results indicate that Npl4 is unique among Cdc48 cofactors and suggest a mechanism for binding and translocation of polyubiquitinated substrates into the ATPase. |
External links | Nat Struct Mol Biol / PubMed:29967539 / PubMed Central |
Methods | EM (single particle) / X-ray diffraction |
Resolution | 2.58233712092 - 8.2 Å |
Structure data | EMDB-7476, PDB-6chs: EMDB-7477: EMDB-7478: EMDB-7479: PDB-6cdd: |
Chemicals | ChemComp-ZN: ChemComp-HOH: ChemComp-AGS: ChemComp-MG: |
Source |
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Keywords | PROTEIN BINDING / AAA ATPase cofactor / zinc finger / MPN / MOTOR PROTEIN / AAA+ / ERAD / ubiquitin-binding protein |