What are protein-protein interactions?
Proteins interact with other proteins in nearly every biological life process making protein expression extremely dynamic. Protein expression is extremely hard to characterize because many proteins are expressed in a cell-dependent manner and the proteins needed for certain tasks aren't always expressed or active. The interaction of two proteins has been characterized as having six specific biological effects: altering the kinetic properties of enzymes, allowing for substrate channeling, creating a new binding site for small molecules, inactivating or destroying a protein, changing the specificity of a protein for its substrate, and/or serving as a regulatory role in either an upstream/downstream event.
A variety of methods are often necessary to characterize and confirm protein-protein interactions. These methods include, but aren't limited to, protein affinity chromatography, affinity blotting, coimmunoprecipitation, cross-linking, two-hybrid system, and phage displays [1].
A variety of methods are often necessary to characterize and confirm protein-protein interactions. These methods include, but aren't limited to, protein affinity chromatography, affinity blotting, coimmunoprecipitation, cross-linking, two-hybrid system, and phage displays [1].
What proteins interact with AAKG2?
The network shown on the left is the protein interactions of AAKG2 (seen in red) that was constructed using the STRING database. The STRING database compiles hundreds of thousands of known and predicted protein interactions taken from a vast array of resources. The number and color of each line between proteins characterizes the support of each protein interaction and how the connection was determined (Table 1 illustrates this). From the extensive number of lines connecting the proteins in the network, it can be said that the protein interactions of AAKG2 and it's functional partners has been very well studied and characterized.
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Analysis
The interaction network of the AAKG2 protein has been very well studied. AAKG2 mostly interacts with proteins in it's protein family including: PRKAA1, PRKAA2, PRKAB1, PRKAB2, PRKAG1 and PRKAG3. The combination of AAKG2 plus these proteins make up the heterotrimeric AMPK protein (see Protein Page). All of these proteins play a role in the regulation of fatty acid synthesis and cholesterol synthesis via phosphorylation. The alpha subunit proteins (PRKAA1 and PRKAA2) are catalytic and also play a role in switching off biosynthetic pathways when ATP levels are low. The beta subunit proteins (PRKAB1 and PRKAB2) are regulatory proteins that are also involved in the regulation of the activity of AMPK. AAKG2 also interacts with a protein called acetyl-Coenzyme A carboxylase beta (ACACB) that is involved in the regulation of fatty acid oxidation. This connection is intuitive because fatty acid oxidation and fatty acid synthesis are both necessary in fatty acid metabolism. Serine/threonine kinase 11 (STK11) is another protein that AAKG2 interacts with and is involved in the activation of the AMPK protein (this connection is explored more in depth in the Future Directions Page). STE20-related kinase adaptor alpha (STRADA) is a protein that also interacts with AAKG2 and is involved in the activation and relocation of the previous protein, STK11. The last protein in the interaction network, Ras homolog enriched in brain (RHEB), is involved in the activation of mTORC1 signaling. This interaction seems logical because mTORC1 signaling is involved in the regulation of cellular responses to fuel availability [2].
References
[1] Phizicky E.M. and Fields S. (1995) Protein-protein interactions: Methods for detection and analysis. Microbiology Review. 59, 94-123
[2] Catania, C., Binder, E., and Cota, D. (2011) mTORC1 signaling in energy balance and metabolic disease. International Journal of Obesisty. 35, 551-761. doi: 10.1038/ljo.2010.208
[3] STRING (Search Tool for the Retrieval of Interacting Genes/Proteins). N.p., n.d. Web 10 May. 2013.
[2] Catania, C., Binder, E., and Cota, D. (2011) mTORC1 signaling in energy balance and metabolic disease. International Journal of Obesisty. 35, 551-761. doi: 10.1038/ljo.2010.208
[3] STRING (Search Tool for the Retrieval of Interacting Genes/Proteins). N.p., n.d. Web 10 May. 2013.
Margaret Beatka ([email protected])
Page Last Updated: 5/10/13
This web page was produced as an assignment for Genetics 677, as an undergraduate course at UW-Madison.
Page Last Updated: 5/10/13
This web page was produced as an assignment for Genetics 677, as an undergraduate course at UW-Madison.