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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
48
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pubmed:dateCreated |
2004-11-23
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pubmed:abstractText |
The AAA ATPase p97/VCP forms complexes with different adapters to fulfill distinct cellular functions. We analyzed the structural organization of the Ufd1-Npl4 adapter complex and its interaction with p97 and compared it with another adapter, p47. We found that the binary Ufd1-Npl4 complex forms a heterodimer that cooperatively interacts with p97 via a bipartite binding mechanism. Binding site 1 (BS1) is a short hydrophobic stretch in the C-terminal domain of Ufd1. The second binding site is located at the N terminus of Npl4 and is activated upon binding of Ufd1 to Npl4. It consists of about 80 amino acids that are predicted to form a ubiquitin fold domain (UBD). Despite the lack of overall homology between Ufd1-Npl4 and p47, both adapters use identical binding mechanisms. Like the ubiquitin fold ubiquitin regulatory X (UBX) domain in p47, the Npl4-UBD interacts with p97 via the loop between its strands 3 and 4 and a conserved arginine in strand 1. Furthermore, we identified a region in p47 homologous to Ufd1-BS1. The UBD/UBX and the BS1 of both adapters interact with p97 independently, whereas homologous binding sites in both adapters compete for binding to p97. In contrast to p47, however, Ufd1-Npl4 does not regulate the ATPase activity of p97; nor does a variant of p47 that contains both binding sites but lacks the N-terminal domains. Therefore, the binding sites alone do not regulate p97 directly but rather serve as anchor points to position adapter-specific domains at critical locations to modulate p97-mediated reactions.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/CDC48 protein,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/NPL4 protein, S cerevisiae,
http://linkedlifedata.com/resource/pubmed/chemical/Npl4 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Nsfl1c protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Pore Complex Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nucleocytoplasmic Transport Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Saccharomyces cerevisiae Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Soluble N-Ethylmaleimide-Sensitive...,
http://linkedlifedata.com/resource/pubmed/chemical/Ufd1l protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Vesicular Transport Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
49609-16
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15371428-Adenosine Triphosphatases,
pubmed-meshheading:15371428-Animals,
pubmed-meshheading:15371428-Binding Sites,
pubmed-meshheading:15371428-Carrier Proteins,
pubmed-meshheading:15371428-Cell Cycle Proteins,
pubmed-meshheading:15371428-Down-Regulation,
pubmed-meshheading:15371428-Mutation,
pubmed-meshheading:15371428-Nuclear Pore Complex Proteins,
pubmed-meshheading:15371428-Nucleocytoplasmic Transport Proteins,
pubmed-meshheading:15371428-Protein Binding,
pubmed-meshheading:15371428-Protein Structure, Tertiary,
pubmed-meshheading:15371428-Proteins,
pubmed-meshheading:15371428-Rats,
pubmed-meshheading:15371428-Saccharomyces cerevisiae Proteins,
pubmed-meshheading:15371428-Soluble N-Ethylmaleimide-Sensitive Factor Attachment...,
pubmed-meshheading:15371428-Vesicular Transport Proteins
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pubmed:year |
2004
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pubmed:articleTitle |
The AAA ATPase p97/VCP interacts with its alternative co-factors, Ufd1-Npl4 and p47, through a common bipartite binding mechanism.
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pubmed:affiliation |
Swiss Federal School of Technology, Institute of Biochemistry, ETH Honggerberg HPM, Zurich 8093, Switzerland.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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