Introduction to Protein InteractionsImportance of Protein Interactions
The study of protein interactions has been vital to the understanding of how proteins function within the cell. Publication of the draft sequence of the human genome and proteomics-based protein profiling studies catalyzed a resurgence in protein interaction analysis. Characterizing the interactions of proteins in a given cellular proteome (now often referred to as the “interactome”) will be the next milestone along the road to understanding the biochemistry of the cell.
The ~ 30,000 genes of the human genome are speculated to give rise to 1 x 10(6) proteins through a series of post-translational modifications and gene-splicing mechanisms. Although a population of these proteins can be expected to work in relative isolation, the majority are expected to operate in concert with other proteins in complexes and networks to orchestrate the myriad of processes that impact cellular structure and function. These processes include cell-cycle control, differentiation, protein folding, signaling, transcription, translation, post-translational modification and transport.
Implications about function can be made via protein:protein interaction studies. These implications are based on the premise that the function of unknown proteins may be discovered if captured through their interaction with a protein target of known function. Consequences of Protein Interactions
The result of two or more proteins interacting with a specific functional objective can be demonstrated in several different ways. The measurable effects of protein interactions have been outlined by Phizicky and Fields (see Recommended Reading List on page 11). Protein interactions can:
• Alter the kinetic properties of enzymes. This may be the result of subtle changes at the level of substrate binding or at the level of an allosteric effect.
• Allow for substrate channeling by moving a substrate between or among subunits, resulting ultimately in an intended end-product.
• Create a new binding site, typically for small effector molecules.
• Inactivate or destroy a protein.
• Change the specificity of a protein for its substrate through interaction with different binding partners; e.g., demonstrate a new function that neither protein can exhibit alone.
• Serve a regulatory role in either an upstream or a downstream action.