6CHS

Cdc48-Npl4 complex in the presence of ATP-gamma-S

Summary for 6CHS

• Entry DOI: 10.2210/pdb6chs/pdb
• Related: 6CDD
• EMDB information: 7476
• Descriptor: Npl4, Putative cell division control protein, ZINC ION, ... (5 entities in total)
• Functional Keywords: aaa+, erad, zinc finger, ubiquitin-binding protein, motor protein
• Biological source: Chaetomium thermophilum (strain DSM 1495 / CBS 144.50 / IMI 039719); More
• Total number of polymer chains: 7
• Total formula weight: 623176.93

Authors

Kim, K.H.,Bodnar, N.O.,Walz, T.,Rapoport, T.A. (deposition date: 2018-02-22, release date: 2018-07-04, Last modification date: 2024-03-13)

Primary citation

Bodnar, N.O.,Kim, K.H.,Ji, Z.,Wales, T.E.,Svetlov, V.,Nudler, E.,Engen, J.R.,Walz, T.,Rapoport, T.A.
Structure of the Cdc48 ATPase with its ubiquitin-binding cofactor Ufd1-Npl4.
Nat. Struct. Mol. Biol., 25:616-622, 2018

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 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.

PubMed: 29967539
DOI: 10.1038/s41594-018-0085-x

Experimental method

ELECTRON MICROSCOPY (4.3 Å)