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HDX-MS of CHIP wt and K30A mutant

ABSTRACT: HDX-MS was used to establish that conformational-inhibition-signals extended from the TPR-domain to the U-box of CHIP. This underscores inter-domain allosteric regulation of CHIP by the core molecular chaperones. Defining the chaperone-associated TPR-domain of CHIP as a manager of inter-domain communication highlights the potential for scaffolding modules to regulate, as well as assemble, complexes that are fundamental to protein homeostatic control.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Kathryn L Ball

PROVIDER: MSV000079205 | MassIVE | Thu Jul 30 22:34:00 BST 2015

SECONDARY ACCESSION(S): PXD003513

REPOSITORIES: MassIVE

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Publications

Protein-Protein Interactions Modulate the Docking-Dependent E3-Ubiquitin Ligase Activity of Carboxy-Terminus of Hsc70-Interacting Protein (CHIP).

Narayan Vikram V Landré Vivien V Ning Jia J Hernychova Lenka L Muller Petr P Verma Chandra C Walkinshaw Malcolm D MD Blackburn Elizabeth A EA Ball Kathryn L KL

Molecular & cellular proteomics : MCP 20150901 11

CHIP is a tetratricopeptide repeat (TPR) domain protein that functions as an E3-ubiquitin ligase. As well as linking the molecular chaperones to the ubiquitin proteasome system, CHIP also has a docking-dependent mode where it ubiquitinates native substrates, thereby regulating their steady state levels and/or function. Here we explore the effect of Hsp70 on the docking-dependent E3-ligase activity of CHIP. The TPR-domain is revealed as a binding site for allosteric modulators involved in determi ...[more]

PMID: 26330542

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