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Structure paper

TitleStructure of the Cdc48 ATPase with its ubiquitin-binding cofactor Ufd1-Npl4.
Journal, issue, pagesNat Struct Mol Biol, Vol. 25, Issue 7, Page 616-622, Year 2018
Publish dateJul 2, 2018
AuthorsNicholas O Bodnar / Kelly H Kim / Zhejian Ji / Thomas E Wales / Vladimir Svetlov / Evgeny Nudler / John R Engen / Thomas Walz / Tom A Rapoport /
PubMed AbstractMany 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 linksNat Struct Mol Biol / PubMed:29967539 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2.58233712092 - 8.2 Å
Structure data

7476

6chs

EMDB-7476, PDB-6chs:
Cdc48-Npl4 complex in the presence of ATP-gamma-S
Method: EM (single particle) / Resolution: 4.3 Å

EMDB-7477:
Cdc48 in the presence of ADP
Method: EM (single particle) / Resolution: 7.2 Å

EMDB-7478:
Cdc48 in the presence of ATP-gamma-S
Method: EM (single particle) / Resolution: 8.2 Å

EMDB-7479:
Cdc48-Npl4 complex in the presence of ADP
Method: EM (single particle) / Resolution: 6.7 Å

PDB-6cdd:
Npl4 zinc finger and MPN domains (Chaetomium thermophilum)
Method: X-RAY DIFFRACTION / Resolution: 2.58233712092 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-HOH:
WATER / Water

ChemComp-AGS:
PHOSPHOTHIOPHOSPHORIC ACID-ADENYLATE ESTER / ATP-gamma-S, energy-carrying molecule analogue*YM

ChemComp-MG:
Unknown entry

Source
  • Chaetomium thermophilum (fungus)
  • chaetomium thermophilum (strain dsm 1495 / cbs 144.50 / imi 039719) (fungus)
KeywordsPROTEIN BINDING / AAA ATPase cofactor / zinc finger / MPN / MOTOR PROTEIN / AAA+ / ERAD / ubiquitin-binding protein

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