Protein-protein interaction
From Wikipedia, the free encyclopedia
Protein-protein interactions refer to the association of protein molecules and the study of these associations from the perspective of biochemistry and networks.
The interactions between proteins are important for many biological functions. For example, signals from the exterior of a cell are mediated to the inside of that cell by protein-protein interactions of the signalling molecules. This process, called signal transduction, plays a fundamental role in many biological processes and in many diseases (e.g. cancer). Proteins might interact for a long time to form part of a protein complex, a protein may be carrying another protein (for example, from cytoplasm to nucleus or vice versa in the case of the nuclear pore importins), or a protein may interact briefly with another protein just to modify it (for example, a protein kinase will add a phosphate to a target protein). This modification of proteins can itself change protein-protein interactions. For example, some proteins with SH2 domains only bind to other proteins when they are phosphorylated on the amino acid tyrosine. In conclusion, protein-protein interactions are of central importance for virtually every process in a living cell. Information about these interactions improves our understanding of diseases and can provide the basis for new therapeutic approaches.
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[edit] Methods to investigate protein-protein interactions
As protein-protein interactions are so important there is a multitude of methods to detect them. Each of the approaches has its own strengths and weaknesses, especially with regard to the sensitivity and specificity of the method. A high sensitivity means that many of the interactions that occur in reality are detected by the screen. A high specificity indicates that most of the interactions detected by the screen are also occurring in reality.
- Co-immunoprecipitation is considered to be the gold standard assay for protein-protein interactions, especially when it is performed with endogenous (not overexpressed and not tagged) proteins. The protein of interest is fished out of the cells with a specific antibody. Interaction partners which stick to this protein are subsequently identified by western blotting. Interactions detected by this approach are considered to be real. However, this method can only verify interactions between suspected interaction partners. Thus, it is not a screening approach.
- The yeast two-hybrid screen investigates the interaction between artificial fusion proteins inside the nucleus of yeast. This approach can fish out binding partners of a protein in an unbiased manner. However, the method has a notorious high false-positive rate which makes it necessary to verify the identified interactions by co-immunoprecipitation.
- Tandem affinity purification (TAP) detects interactions within the correct cellular environment (e.g. in the cytosol of a mammalian cell) (Rigaut et al., 1999). This is a big advantage compared to the yeast two-hybrid approach. However, the TAP tag method requires two successive steps of protein purification. Thus, it can not readily detect transient protein-protein interactions.
- Quantitative immunoprecipitation combined with knock-down (QUICK) relies on co-immunoprecipitation, quantitative mass spectrometry (SILAC) and RNA interference (RNAi). This method detects interactions among endogenous non-tagged proteins (Selbach and Mann, 2006). Thus, it has the same high confidence as co-immunoprecipitation. However, this method also depends on the availability of suitable antibodies.
[edit] Protein interaction databases
- BioGRID is a public repository for protein and genetic interactions. [1]
- HPRD Human Protein Reference Database a (manually) curated database of human protein information with visualization tools.
- The MIPS Mammalian Protein-Protein Interaction Database
- IntAct Interaction Database is a public repository for manually curated molecular interaction data from literature.
- APID Agile Protein Interaction DataAnalyzer is an interactive bioinformatics web tool to explore and analyze in a unified and comparative platform main currently known information about protein–protein interactions.
[edit] Protein-protein interaction network visualization
Visualization of protein-protein interaction networks is a popular application of Scientific_visualization techniques. Although protein interaction diagrams are common in textbooks, diagrams of whole cell protein interaction networks were not as common since the level of complexity made them difficult to generate. One example of a manually produced molecular interaction map is Kurt Kohn's 1999 map of cell cycle control. [Mol Biol Cell. 1999] Drawing on Kohn's map, in 2000 Schwikowski, Uetz, and Fields published a paper on protein-protein interactions in yeast, linking together 1,548 interacting proteins determined by two-hybrid testing. They used a force-directed (Sugiyama) graph drawing algorithm to automatically generate an image of their network. [Nature 2000]. Since then, many other systems have been developed allowing for the automatic visualization of protein-protein interaction networks, including:
Many of the protein interaction databases mentioned above now contain visualization tools to help users navigate the data.
[edit] See also
Protein-protein interaction prediction
[edit] References
- Rigaut G, Shevchenko A, Rutz B, Wilm M, Mann M, Seraphin B (1999) A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol. 17:1030-2. PMID: 10504710
- Selbach M, Mann M. (2006) Protein interaction screening by quantitative immunoprecipitation combined with knockdown (QUICK). Nat Methods. 3:981-3. PMID: 17072306
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