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PubMed · 17202270

Structural insights into the p97-Ufd1-Npl4 complex.

Valerie E Pye·Fabienne Beuron·Catherine A Keetch·Ciaran McKeown·Carol V Robinson·Hemmo H Meyer·Xiaodong Zhang·Paul S Freemont
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Abstract

p97/VCP (Cdc48 in yeast) is an essential and abundant member of the AAA+ family of ATPases and is involved in a number of diverse cellular pathways through interactions with different adaptor proteins. The two most characterized adaptors for p97 are p47 and the Ufd1 (ubiquitin fusion degradation 1)-Npl4 (nuclear protein localization 4) complex. p47 directs p97 to membrane fusion events and has been shown to be involved in protein degradation. The Ufd1-Npl4 complex directs p97 to an essential role in endoplasmic reticulum-associated degradation and an important role in mitotic spindle disassembly postmitosis. Here we describe the structural features of the Ufd1-Npl4 complex and its interaction with p97 with the aid of EM and other biophysical techniques. The Ufd1-Npl4 heterodimer has an elongated bilobed structure that is approximately 80 x 30 A in dimension. One Ufd1-Npl4 heterodimer is shown to interact with one p97 hexamer to form the p97-Ufd1-Npl4 complex. The Ufd1-Npl4 heterodimer emanates from one region on the periphery of the N-D1 plane of the p97 hexamer. Intriguingly, the p97-p47 and the p97-Ufd1-Npl4 complexes are significantly different in stoichiometry, symmetry, and quaternary arrangement, reflecting their specific actions and their ability to interact with additional cofactors that cooperate with p97 in diverse cellular pathways.

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Adenosine TriphosphatasesDimerizationEndoplasmic ReticulumMicroscopy, ElectronModels, MolecularMultiprotein ComplexesNuclear Pore Complex ProteinsNuclear ProteinsNucleocytoplasmic Transport ProteinsProtein BindingProtein Structure, QuaternaryRecombinant ProteinsSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsUbiquitinVesicular Transport ProteinsJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, Non-P.H.S.

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Valerie E Pye, Fabienne Beuron, Catherine A Keetch, Ciaran McKeown, Carol V Robinson, Hemmo H Meyer, Xiaodong Zhang, Paul S Freemont. 2007-01-03. Structural insights into the p97-Ufd1-Npl4 complex.. https://doi.org/10.1073/pnas.0603408104

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