Biology: The Thermodynamics of Protein-Protein Interactions

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There are various methods that have been developed over these years to study protein-protein interactions (PPIs). PPI plays a big role in the cell-signalling cascade; for instance, dephosphorylation of glycogen synthase by protein phosphatase-1 results in glycogen synthesis. To know whether a specific protein binds to its partner, for example, whether TFIIH interacts with TFIIE or TFIIF to complete the pre-initiation complex in transcription, different methods such as co-immunoprecipitation (co-IP), glutathione-S-transferase (GST) pull down assays, yeast-two-hybrid (Y2H) assays, isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), nuclear magnetic resonance (NMR) spectroscopy and etc. can be use to validate PPIs. Yet, doing one experiment using one method is not enough to validate the PPI between two or more proteins. Factors such as overexpression of proteins and manipulation of the agents used in the experiment could result in a bias data. Thus, the results should be unbiased by incorporating different methods in the experiment to validate the PPI. In this essay, the different methods will be described and the factors that cause the different methods giving rise to different results will be discussed. Co-IP is the most commonly used methods to verify protein-protein interactions (Berggård et al., 2007). Antibodies that are specific to the bait complexes are used to capture the bait complexes in a cell lysate shown in Fig. 1. The antibody is immobilized on Protein A/G, which is covalently bound to the agarose beads. Since the antibody is specific to only the bait complex, the antibody will not bind to other proteins found in the cell lysate, and hence, these proteins will be wash off. The antibody-bait compl... ... middle of paper ... ...nflammatory Arthritis in Mice. Science. 332 (6028), pp. 478-484. Wissmueller S., Font J., Liew C.W., Cram E., Schroeder T., Turner J., Crossley M., Mackay J.P. and Matthews J.M. (2011). Protein-protein interactions: analysis of a false positive GST pulldown result. Proteins. 79 (8), pp. 2365-2371. Yu H. (1999). Extending the size limit of protein nuclear magnetic resonance. Proceedings of the National Academy of Sciences. 96 (2), pp. 332-334. Zhang X., Tang H., Ye C. and Liu M. (2006). Structure-based drug design: NMR-based approach for ligand-protein interactions. Drug Discovery Today: Technologies. 3 (3), pp. 241-245. Zhou YL., Liao JM., Du F. and Liang Yi. (2005). Thermodynamics of the interaction of xanthine oxidase with superoxide dismutase studied by isothermal titration calorimetry and fluorescence spectroscopy. Thermochimica Acta. 426 (1-2), pp. 173-178.

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