DataSets / Project home (HSP90 cochaperone network)
A quantitative chaperone interaction network for exploring the wiring of cellular protein folding pathways
First Author: Mikko Taipale (
  Chaperones are abundant cellular proteins that promote the folding and function of their substrate proteins, or clients. In vivo, chaperones also associate with a large and diverse set of co-chaperones that regulate their specificity and function. However, how these co-chaperones regulate protein folding and whether they have Hsp90- or Hsp70-independent biological functions is still poorly understood for most co-chaperones and substrates. Here, we combine mass spectrometry and a quantitative high-throughput LUMIER assay to explore the chaperone/ cochaperone/ client interaction network in human cells. We uncover hundreds of novel chaperone clients and characterize their integration into specific co-chaperone complexes. As a salient example of the power of such analysis, we show that convergent evolution of β-propeller folds has co-occurred with divergent evolution of β-propeller-specific NUDC family co-chaperones, suggesting that the evolution of these abundant protein folds has been facilitated by specialized co-chaperones. We provide a comprehensive framework for understanding how the proteostasis network is regulated and a resource for exploring how it changes in development and disease.

Manuscript available at PubMed Central and at Cell.

Interaction data was deposited in IntAct and BioGRID

The raw mass spectrometry data was contributed to ProteomeXchange through the MassIVE repository dataset 1, dataset 2, dataset 3, dataset 4.