Protein Domains are distinct functional and structural units in a protein that form compact three-dimensional structures. They are often responsible for a particular function or interaction which contributes to the overall role of a protein. [1] Similar domains can be found in proteins with different functions as a result of domains existing in a variety of biological contexts. They can be combined in different arrangements to produce proteins with different functions. [1]
What domains are found in TCF4?
Pfam,SMART,InterPRo, and PROSITE were used in order to search for protein domains found in TCF4. The different sites were used in order to evaluate how consistently protein domains were identified across programs. The outputs for TCF4 were quite consistent across the platforms. Results from Pfam and SMART are displayed below:
Results from Pfam
Results from SMART
Pfam and SMART both identified one protein domain, the basic helix-loop-helix DNA-binding domain (bHLH), throughout all 11 model organisms used. bHLH proteins form a large family of transcriptional regulators found in organisms from yeast to humans. [2] They are important for critical developmental processes such as the development of the nervous system and muscles. The bHLH motif is characterized by two alpha-helices connected by a loop. bHLH proteins typically bind to an E-box. Transcription factors that contain this domain are dimeric, each with one helix with basic amino acid residues that facilitate DNA-binding. [3]
Figure 1. Dimeric form of the bHLH protein domain
How conserved is the bHLH domain in TCF4?
Figure 2. Domain Structure of TCF4 homologs
The domain structure of the TCF4 gene is well conserved in organisms ranging from Caenorhabditis elegans to Homo sapiens with the consistent presence of the helix-loop-helix DNA-binding domain.
Conclusion
When comparing TCF4 domains across the various model organisms, there were high levels of conservation observed. The basic helix-loop-helix DNA-binding domain was present in all model organisms. This reveals that TCF4 plays an important role in DNA-binding activities, in particular with genes such as MATH1, which is further discussed in the specific aims section of this website. The conserved presence of bHLH in the TCF4 gene implies a correlation between TCF4 DNA-binding activities and the occurrence of Pitt-Hopkins Syndrome.
References Header:http://www.sciencemag.org/custom-publishing/webinars/unlocking-elusive-mind-role-protein-biomarkers-understanding [1] EMBL-EBI. (n.d.). What are protein domains? Retrieved from https://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains [2]Jones, S. (2004). An overview of the basic helix-loop-helix proteins. Genome Biology, 5(6), 226. http://doi.org/10.1186/gb-2004-5-6-226 [3]Pfam Homepage. (n.d.). Retrieved March 1, 2018, from http://pfam.xfam.org/
Figure 1.http://doi.org/10.1186/gb-2004-5-6-226
This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.