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| Subject | Predicate | Object |
|---|---|---|
| http://purl.uniprot.org/citations/26475856 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26475856 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/26475856 | http://www.w3.org/2000/01/rdf-schema#comment | "Valosin-containing protein/p97 is an ATP-driven protein segregase that cooperates with distinct protein cofactors to control various aspects of cellular homeostasis. Mutations at the interface between the regulatory N-domain and the first of two ATPase domains (D1 and D2) deregulate the ATPase activity and cause a multisystem degenerative disorder, inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia/amyotrophic lateral sclerosis. Intriguingly, the mutations affect only a subset of p97-mediated pathways correlating with unbalanced cofactor interactions and most prominently compromised binding of the ubiquitin regulatory X domain-containing protein 1 (UBXD1) cofactor during endolysosomal sorting of caveolin-1. However, how the mutations impinge on the p97-cofactor interplay is unclear so far. In cell-based endosomal localization studies, we identified a critical role of the N-terminal region of UBXD1 (UBXD1-N). Biophysical studies using NMR and CD spectroscopy revealed that UBXD1-N can be classified as intrinsically disordered. NMR titration experiments confirmed a valosin-containing protein/p97 interaction motif and identified a second binding site at helices 1 and 2 of UBXD1-N as binding interfaces for p97. In reverse titration experiments, we identified two distant epitopes on the p97 N-domain that include disease-associated residues and an additional interaction between UBXD1-N and the D1D2 barrel of p97 that was confirmed by fluorescence anisotropy. Functionally, binding of UBXD1-N to p97 led to a reduction of ATPase activity and partial protection from proteolysis. These findings indicate that UBXD1-N intercalates into the p97-ND1 interface, thereby modulating interdomain communication of p97 domains and its activity with relevance for disease pathogenesis. We propose that the polyvalent binding mode characterized for UBXD1-N is a more general principle that defines a subset of p97 cofactors."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m115.680686"xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m115.680686"xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Meyer H."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Meyer H."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Bayer P."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Bayer P."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Matena A."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Matena A."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Trusch F."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Trusch F."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Freemont P.S."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Freemont P.S."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Vuk M."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Vuk M."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Koerver L."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Koerver L."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Knaevelsrud H."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/author | "Knaevelsrud H."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/date | "2015"xsd:gYear |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |
| http://purl.uniprot.org/citations/26475856 | http://purl.uniprot.org/core/name | "J. Biol. Chem."xsd:string |