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http://purl.uniprot.org/citations/23865999http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23865999http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/23865999http://www.w3.org/2000/01/rdf-schema#comment"The E3 ubiquitin ligase CHIP (C-terminus of Hsc70 Interacting Protein, a 70 kDa homodimer) binds to the molecular chaperone Hsc70 (a 70 kDa monomer), and this complex is important in both the ubiquitination of Hsc70 and the turnover of Hsc70-bound clients. Here we used NMR spectroscopy, biolayer interferometry, and fluorescence polarization to characterize the Hsc70-CHIP interaction. We found that CHIP binds tightly to two molecules of Hsc70 forming a 210 kDa complex, with a Kd of approximately 60 nM, and that the IEEVD motif at the C-terminus of Hsc70 (residues 642-646) is both necessary and sufficient for binding. Moreover, the same motif is required for CHIP-mediated ubiquitination of Hsc70 in vitro, highlighting its functional importance. Relaxation-based NMR experiments on the Hsc70-CHIP complex determined that the two partners move independently in solution, similar to "beads on a string". These results suggest that a dynamic C-terminal region of Hsc70 provides for flexibility between CHIP and the chaperone, allowing the ligase to "search" a large space and engage in productive interactions with a wide range of clients. In support of this suggestion, we find that deleting residues 623-641 of the C-terminal region, while retaining the IEEVD motif, caused a significant decrease in the efficiency of Hsc70 ubiquitination by CHIP."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.org/dc/terms/identifier"doi:10.1021/bi4009209"xsd:string
http://purl.uniprot.org/citations/23865999http://purl.org/dc/terms/identifier"doi:10.1021/bi4009209"xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Southworth D.R."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Southworth D.R."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Smith M.C."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Smith M.C."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Zuiderweg E.R."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Zuiderweg E.R."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Scaglione K.M."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Scaglione K.M."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Gestwicki J.E."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Gestwicki J.E."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Patury S."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Patury S."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Paulson H.L."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Paulson H.L."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Dickey C.A."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Dickey C.A."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Assimon V.A."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Assimon V.A."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Thompson A.D."xsd:string
http://purl.uniprot.org/citations/23865999http://purl.uniprot.org/core/author"Thompson A.D."xsd:string