Abstract
Understanding the functions of proteins requires information about their protein-protein interactions (PPI). The collective effort of the scientific community generates far more data on any given protein than individual experimental approaches. The latter are often too limited to reveal an interactome comprehensively. We developed a workflow for parallel mining of all major PPI databases, containing data from several model organisms, and to integrate data from the literature for a protein of interest. We applied this novel approach to build the PPI network of the human Hsp90 molecular chaperone machine (Hsp90Int) for which previous efforts have yielded limited and poorly overlapping sets of interactors. We demonstrate the power of the Hsp90Int database as a discovery tool by validating the prediction that the Hsp90 co-chaperone Aha1 is involved in nucleocytoplasmic transport. Thus, we both describe how to build a custom database and introduce a powerful new resource for the scientific community.
Highlights
The comprehensive determination of the interactome of a protein of interest (POI) is technically challenging and in many cases impossible, even though it is indispensable to understand its functions
To construct the interactome of the human Hsp90 molecular chaperone machine from available data, we decided to use all the major public protein-protein interactions (PPI) databases [29], even when the data came from different model organisms
We have presented a novel workflow to assemble the virtual interactome of a POI from the vast amount of data that are already available in a variety of public databases
Summary
The comprehensive determination of the interactome of a protein of interest (POI) is technically challenging and in many cases impossible, even though it is indispensable to understand its functions. It has been speculated that the Hsp chaperone machine may assist up to 10% of all cytosolic proteins at some stage of their life cycle [5], but how it recognizes its substrates and, in most cases, what it does to them remain very poorly understood. Most likely because of the central role of Hsp in many cellular processes, cancer cells, pathogens, and viruses may be dependent on it. This has led to a great interest in developing specific Hsp inhibitors, of which several are in clinical trials for the treatment of cancer [6,7]
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