This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What are Post-Translational Modifications?
Post-translational modifications are changes in the genome that occur after the protein has been created by the ribosome. These changes can include the addition of functional groups via covalent bonds, cleavage of parts of the protein, or even degradation of a protein. These changes allow even more variations of proteins to be created and diversify the structure and function of the proteome. [1] Examples of the types of pot-translational modifications that can occur when a residue or functional group are added are below:
Protein Phosphorylation
Protein phosphorylation is a post-translational modification which adds a phosphate group to an amino acid. This usually serves to turn the protein on or off and is a common mechanism regulating protein activity in the body.
Phosphorylation of MTHFR
NetPhos is a database that can help identify phosphorylation sites in specific proteins from many different organisms. NetPhos was used to identify phosphorylation sites in Humans, zebrafish, and C. elegans. Zebrafish were investigated because they are the model organism for this project. C. elegans was chosen to see if phosphorylation patterns vary significantly between vertebrates and invertebrates. The red lines on the graphs below are phosphorylated serine residues, green are phosphorylated threonine residues, and blue are phosphorylated tyrosine residues. Any bars that extend above the pink line have a high potential of being true phosphorylation sites.
Humans
Zebrafish
C. elegans
Discussion
In both humans and zebrafish, residues 30-50 have very high probability of serine phosphorylation. This is seen to a much lesser extent in C . elegans. This region is 3' of the MTHFR domain on MTHFR. The discrepancies between vertebrates and invertebrates also suggest that this could be involved in neurulation or functioning of the spinal cord and nervous system. The role of phoshorylation in regulating MTHFR and how this contributes to healthy neural tube closure is unknown and will be the focus of this project.
References:
[1] Thermo Fisher Scientific. Overview of Post-Translational Modifications (PTM). Retrieved 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
Images:
Header:https://bgr.com/2017/10/09/dna-editing-nasa-mars-astronauts/
Image 1: http://tcohenlab.web.unc.edu/tau-post-translational-modification-puzzle/post-translational-modifications-ptm/
Images 2-4: http://www.cbs.dtu.dk/services/NetPhos/
[1] Thermo Fisher Scientific. Overview of Post-Translational Modifications (PTM). Retrieved 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
Images:
Header:https://bgr.com/2017/10/09/dna-editing-nasa-mars-astronauts/
Image 1: http://tcohenlab.web.unc.edu/tau-post-translational-modification-puzzle/post-translational-modifications-ptm/
Images 2-4: http://www.cbs.dtu.dk/services/NetPhos/