Post-Translational Modifications |
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What are post-translational modifications?
Protein post-translational modifications (PTMs) increase the functional diversity of the proteome by the covalent addition of functional groups or proteins, proteolytic cleavage of regulatory subunits, or degradation of entire proteins. Therefore, identifying and understanding PTMs is critical in the study of cell biology and disease treatment and prevention. [1] The increase in complexity from the level of the genome to the proteome is further facilitated by protein post-translational modifications (PTMs). PTMs are chemical modifications that play a key role in functional proteomic because they regulate activity, localization, and interaction with other cellular molecules such as proteins, nucleic acids, lipids and cofactors. [1]
What are the different types of post-transcriptional modifications?
Post-transcriptional modifications include phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation and proteolysis and influence almost all aspects of normal cell biology and pathogenesis. [1]
NRXN3 Phosphorylation
NetPhos is a good tool to use to recognize true phosphorylation sites in your protein of interest. [2] The two figures with red lines indicate serine phosphorylation sites in both humans and Drosophila melanogaster. The lines above the pink threshold have a high level of confidence in being true phosphorylation sites.
Conclusion
I will be focusing primarily on serine phosphorylation sites in this study. This is because the CASK protein (Calcium/calmodulin-dependent serine protein kinase) that was identified as an interacting protein with NRXN3 also functions in phosphorylating neurexins like NRXN3. [3] For this reason, I believe that there is a some sort of connection between alcohol dependence, the expression of NRXN3, and the phosphorylation between CASK and NRXN3. Mutating those serine sites could result in expression of a mutant uncoordinated fly. This would lead me to think that when NRXN3's serine sites are mutated, CASK levels are low because it cannot phosphorylate NRXN3. This would result in improper synaptic function and the uncoordinated phenotype.
References
[1] Overview of Post-Translational Modifications (PTMs). (n.d.). Retrieved April 13, 2018, from https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/overview-post-translational-modification.html
[2] NetPhos 3.1 Server. (n.d.). Retrieved from http://www.cbs.dtu.dk/services/NetPhos/
[3] Südhof, T. C. (2017). Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits. Cell, 171(4), 745-769. doi:10.1016/j.cell.2017.10.024
Images
Header: https://media.wired.com/photos/595152586b76bb7625b89e58/master/w_2562,c_limit/GenomeTesting-468428788-%5BConverted%5D.jpg
Figure 1: https://www.thermofisher.com/content/dam/LifeTech/Images/integration/Proteome-Complexity-Figure-650px.jpg
Figure 2: https://rockland-inc.com/uploadedImages/ProductsStatic/post-translational-modifications-ptm.gif
[1] Overview of Post-Translational Modifications (PTMs). (n.d.). Retrieved April 13, 2018, from https://www.thermofisher.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/overview-post-translational-modification.html
[2] NetPhos 3.1 Server. (n.d.). Retrieved from http://www.cbs.dtu.dk/services/NetPhos/
[3] Südhof, T. C. (2017). Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits. Cell, 171(4), 745-769. doi:10.1016/j.cell.2017.10.024
Images
Header: https://media.wired.com/photos/595152586b76bb7625b89e58/master/w_2562,c_limit/GenomeTesting-468428788-%5BConverted%5D.jpg
Figure 1: https://www.thermofisher.com/content/dam/LifeTech/Images/integration/Proteome-Complexity-Figure-650px.jpg
Figure 2: https://rockland-inc.com/uploadedImages/ProductsStatic/post-translational-modifications-ptm.gif