ArticleBiochemistry2013
The E3 ubiquitin ligase CHIP and the molecular chaperone Hsc70 form a dynamic, tethered complex.
Article in Biochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 60 citations in OpenAlex.
- Functional and structural analyses of UbcH5 mutants with enhanced binding to the E3 ubiquitin ligase CHIP.Biochemical and biophysical research communications · 2025Article
- Chaperone-dependent and chaperone-independent functions of carboxylate clamp tetratricopeptide repeat (CC-TPR) proteins.Trends in biochemical sciences · 2025Review
- Phosphorylation of tau at a single residue inhibits binding to the E3 ubiquitin ligase, CHIP.Nature communications · 2024Article
- Recognition and reprogramming of E3 ubiquitin ligase surfaces by α-helical peptides.Nature communications · 2023Article
- The molecular basis of spinocerebellar ataxia type 48 caused by a de novo mutation in the ubiquitin ligase CHIP.The Journal of biological chemistry · 2022Article
- Chemical Regulation of the Protein Quality Control E3 Ubiquitin Ligase C-Terminus of Hsc70 Interacting Protein (CHIP).Chembiochem : a European journal of chemical biology · 2022Article
- The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state.Molecular cell · 2021Article
- Cytosolic protein quality control machinery: Interactions of Hsp70 with a network of co-chaperones and substrates.Experimental biology and medicine (Maywood, N.J.) · 2021Review
- Dicarbonyl stress, protein glycation and the unfolded protein response.Glycoconjugate journal · 2021Review
- UbcH5 Interacts with Substrates to Participate in Lysine Selection with the E3 Ubiquitin Ligase CHIP.Biochemistry · 2020Article
- Feedback inhibition of cAMP effector signaling by a chaperone-assisted ubiquitin system.Nature communications · 2019Article
- The cochaperone CHIP marks Hsp70- and Hsp90-bound substrates for degradation through a very flexible mechanism.Scientific reports · 2019Article
- HSP70 is required for the proper assembly of pericentriolar material and function of mitotic centrosomes.Cell division · 2019Article
- The disorderly conduct of Hsc70 and its interaction with the Alzheimer's-related Tau protein.The Journal of biological chemistry · 2018Article
- Protein-Protein Interactions in the Molecular Chaperone Network.Accounts of chemical research · 2018Review
- Protein cross-linking capillary electrophoresis at increased throughput for a range of protein-protein interactions.The Analyst · 2018Article
- Most mutations that cause spinocerebellar ataxia autosomal recessive type 16 (SCAR16) destabilize the protein quality-control E3 ligase CHIP.The Journal of biological chemistry · 2018Article
- Real-time detection of N-end rule-mediated ubiquitination via fluorescently labeled substrate probes.The New phytologist · 2018Article
- Tylophorine Analogs Allosterically Regulates Heat Shock Cognate Protein 70 And Inhibits Hepatitis C Virus Replication.Scientific reports · 2017Article
- Backbone and methyl resonance assignments of the 42 kDa human Hsc70 nucleotide binding domain in the ADP state.Biomolecular NMR assignments · 2017Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.