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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2011-6-7
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pubmed:databankReference |
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pubmed:abstractText |
The hexameric AAA ATPase p97 is involved in several human proteinopathies and mediates ubiquitin-dependent protein degradation among other essential cellular processes. Via its N-terminal domain (N domain), p97 interacts with multiple regulatory cofactors including the UFD1/NPL4 heterodimer and members of the "ubiquitin regulatory X" (UBX) domain protein family; however, the principles governing cofactor selectivity remain to be deciphered. Our crystal structure of the FAS-associated factor 1 (FAF1)UBX domain in complex with the p97N domain reveals that the signature Phe-Pro-Arg motif known to be crucial for interactions of UBX domains with p97 adopts a cis-proline configuration, in contrast to a cis-trans mixture we derive for the isolated FAF1UBX domain. Biochemical studies confirm that binding critically depends on a proline at this position. Furthermore, we observe that the UBX proteins FAF1 and UBXD7 only bind to p97-UFD1/NPL4, but not free p97, thus demonstrating for the first time a hierarchy in p97-cofactor interactions.
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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/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Triphosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Coenzymes,
http://linkedlifedata.com/resource/pubmed/chemical/FAF1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NPLOC4 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/UBXD7 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/UFD1L protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitinated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/p97 ATPase
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1878-4186
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pubmed:author |
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pubmed:copyrightInfo |
Copyright © 2011 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:day |
8
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pubmed:volume |
19
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
833-43
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pubmed:meshHeading |
pubmed-meshheading:21645854-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:21645854-Adenosine Triphosphatases,
pubmed-meshheading:21645854-Amino Acid Motifs,
pubmed-meshheading:21645854-Amino Acid Sequence,
pubmed-meshheading:21645854-Calorimetry,
pubmed-meshheading:21645854-Carrier Proteins,
pubmed-meshheading:21645854-Chromatography, Gel,
pubmed-meshheading:21645854-Coenzymes,
pubmed-meshheading:21645854-Conserved Sequence,
pubmed-meshheading:21645854-Crystallography, X-Ray,
pubmed-meshheading:21645854-Humans,
pubmed-meshheading:21645854-Molecular Sequence Data,
pubmed-meshheading:21645854-Nuclear Proteins,
pubmed-meshheading:21645854-Protein Binding,
pubmed-meshheading:21645854-Protein Interaction Domains and Motifs,
pubmed-meshheading:21645854-Protein Structure, Quaternary,
pubmed-meshheading:21645854-Protein Structure, Tertiary,
pubmed-meshheading:21645854-Proteins,
pubmed-meshheading:21645854-Surface Properties,
pubmed-meshheading:21645854-Titrimetry,
pubmed-meshheading:21645854-Ubiquitin,
pubmed-meshheading:21645854-Ubiquitinated Proteins
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pubmed:year |
2011
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pubmed:articleTitle |
Hierarchical binding of cofactors to the AAA ATPase p97.
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pubmed:affiliation |
Rudolf Virchow Center for Experimental Biomedicine, University of Würzburg, Josef-Schneider-Str. 2, 97080 Würzburg, Germany. petra.haenzelmann@virchow.uni-wuerzburg.de
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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