Protein-protein interaction databases: keeping up with growing interactomes
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Protein –protein interaction databases: Keeping up with growing interactomes Benjamin Lehne and Thomas Schlitt* Department of Medical and Molecular Genetics, Kings College London, 8th Floor Tower Wing, Guy’s Campus, London, SE1 9RT, UK *Correspondence to: Tel: þ44 20 7188 9072; Fax: þ44 20 7188 2585; E-mail: [email protected] Date received (in revised form): 30th January 2009
Abstract Over the past few years, the number of known protein –protein interactions has increased substantially. To make this information more readily available, a number of publicly available databases have set out to collect and store protein– protein interaction data. Protein– protein interactions have been retrieved from six major databases, integrated and the results compared. The six databases (the Biological General Repository for Interaction Datasets [BioGRID], the Molecular INTeraction database [MINT], the Biomolecular Interaction Network Database [BIND], the Database of Interacting Proteins [DIP], the IntAct molecular interaction database [IntAct] and the Human Protein Reference Database [HPRD]) differ in scope and content; integration of all datasets is non-trivial owing to differences in data annotation. With respect to human protein –protein interaction data, HPRD seems to be the most comprehensive. To obtain a complete dataset, however, interactions from all six databases have to be combined. To overcome this limitation, meta-databases such as the Agile Protein Interaction Database (APID) offer access to integrated protein –protein interaction datasets, although these also currently have certain restrictions. Keywords: protein –protein interactions, PPI, database, bioinformatics, IMEx, PSI-MI
The nature of protein –protein interaction data Proteins do not act independently but in a network of complex molecular interactions. Therefore, it is important to identify physical interactions between proteins. Different experimental techniques have been developed to measure physical interactions between proteins; these methods vary considerably, not least in terms of the data they produce. To give some examples, two widely used methods adapted for high-throughput approaches are the yeast two-hybrid (Y2H) system1 and affinity purification followed by mass spectrometry (AP-MS).2 The Y2H system assays whether two proteins physically interact with each other (Figure 1). Genetically modified yeast strains are used to
express a ‘bait’ and a ‘prey’ protein, which, if they interact, trigger the expression of a reporter gene. The method has been used for large-scale screening studies of a variety of model organisms, including yeast, fly and humans. In an AP-MS experiment, a protein of interest is fused to a protein fragment (the ‘tag’), which allows its purification (Figure 2). This modified or tagged protein is expressed and purified from the cell extract using the tag — for example, by antibodies binding specifically to the tag. Proteins binding the tagged protein are co-purified and subsequently identified by MS. The most wid
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