6chs

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

Loading... Status: waiting for Mol* initialization Structural highlights 6chs is a 7 chain structure with sequence from Chatd. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: AGS, MG, ZN Related: 6cdd Gene: CTHT_0009420 (CHATD), CTHT_0027280 (CHATD) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed 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(2+)-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. Structure of the Cdc48 ATPase with its ubiquitin-binding cofactor Ufd1-Npl4.,Bodnar NO, Kim KH, Ji Z, Wales TE, Svetlov V, Nudler E, Engen JR, Walz T, Rapoport TA Nat Struct Mol Biol. 2018 Jul;25(7):616-622. doi: 10.1038/s41594-018-0085-x. Epub, 2018 Jul 2. PMID:29967539 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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