NOTCH1 Protein
What are post-translational modifications?
Recently, studies interrogating the proteome of model organisms have illustrated the vast diversity of changes following transcription and provided evidence for millions of proteins stemming from a much smaller number of genes [1]. Post-translational modifications including the addition of phosphates, carbohydrates, ubiquitins, methyl groups, nitrogen groups, acetyl groups, and lipids not only increases the global diversity of proteins but contributes to activity, localization, and interaction [1].
How is NOTCH1 modified?
A comparison (human on the left, zebrafish on the right) of global phosphorylation without kinase type specified [2].
Global phosphorylation comparison (human on the left, zebrafish on the right) with kinase specificity (serine in red, threonine in green, and tyrosine in blue) [2]. Serine phosphorylation is ubiquitous and found primarily at the C-terminal whereas threonine and tyrosine phosphorylation is concentrated mainly in the EGF-like domains [2]. There is also less threonine and tyrosine phosphorylation around the transmembrane area of NOTCH1 [2].
N-glycosylation (top) [3] and O-linked beta-N-acetylglucosamination (bottom) [4] comparison for humans (left) and zebrafish (right). While N-glycosylation seems to mostly be constricted to the intracellular domain and O-linked beta-N-aceylglucosamination is found throughout NOTCH1, there are no glaring inconsistencies between the two organisms [3-4].
Conclusion
Post-translational modifications drastically increase the complexity of the cellular environment. NOTCH1 is heavily modified and it is likely that disruption of the amino acids normally modified will lead to impaired or aberrant protein function. We can observe that serine phosphorylation is key to C-terminal function or structure while threonine and tyrosine may be more important to the EGF-like domains. In the same way, other modifications can be analyzed and the conservation of these modifications may reveal their role in heart development.
Other post-translational modifications:
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
zebrafish_o-gly_7.jpg | |
File Size: | 29 kb |
File Type: | jpg |