This web page was produced as an assignment for Genetics 564, an undergraduate capstone course at UW-Madison.
What is a domain?
Proteins are composed of strings of amino acids, which then fold to form functional structures. [2] A protein domain is a specific functional area of a protein. Proteins may have many domains, or just one. [3] These domains contribute to how the protein behaves and carries out its necessary functions. Domains may be similar across proteins, and carry out similar or different functions. Domains help proteins become signaling molecules, and interact with other proteins. [3] TGFB1 has domains that allow it to accomplish both of these integral functions. [4]
What domains are in human TGFB1?
TGFB1 has two protein domains, the propeptide domain, as well as the TGFB domain.
Propeptide: The 232 amino acid long propeptide domain is, interestingly, part of the preprotein, before TGFB1 enters it's activated form. This domain takes up a good majority of the entire 390 amino acid long protein, and is notably used for tagging the protein for secretion.
TGFB1: The 97 amino acid long TGFB1 domain is responsible for most of the molecular function of the TGFB1 protein, including interaction with other proteins. This is the part of the protein that is most responsible for signaling to the immune system and causing allergic rhinitis.
Propeptide: The 232 amino acid long propeptide domain is, interestingly, part of the preprotein, before TGFB1 enters it's activated form. This domain takes up a good majority of the entire 390 amino acid long protein, and is notably used for tagging the protein for secretion.
TGFB1: The 97 amino acid long TGFB1 domain is responsible for most of the molecular function of the TGFB1 protein, including interaction with other proteins. This is the part of the protein that is most responsible for signaling to the immune system and causing allergic rhinitis.
What domains does TGFB1 have in other species?
TGFB1 has the same domains in many other species! Here are a few homologs of TGFB1. These species have various protein lengths, but the domains are conserved. Below is the protein layout of a handful of different species' TGFB1 homologs: Humans, mice, rats, zebra fish and fruit flies. It's interesting to understand that, while these species do not necessarily share the physiology involved in allergic rhinitis, they do all have a similarly functioning protein. This is due to the large number of biological pathways, other than allergies, that TGFB1 is involved in. However we can use physiological differences in species to explore allergic or inflammatory pathways similar to our own, as well as vastly different.
Analysis
Protein domains provide us with an interesting and unique breakdown of a protein's structure and function. Two points to highlight from the domain analysis of TGFB1 are:
1. The propeptide section of the protein is much larger than the functional TGFB1 domain of the protein.
2. The two domains are highly conserved across species and evolutionary pressure
The length of the propeptide is something to consider when we think about the nature of the TGFB1 protein. Its a secreted molecule, that is released from one cell and binds to the membrane receptor of another. Therefore, it would be logical for such a mobile protein to be on the smaller side. The propeptide allows the protein to be translated as a nonfunctional molecule, and also helps the protein be directed and gain its function when it's needed.
The fact that the two domains are highly conserved across species tells us that the various pathways that TGFB1 is involved in are pretty universal. It also provides us with a good idea of how ancient the protein is and how it has changed over time. If you're interested in that aspect of the protein, visit the phylogeny page.
1. The propeptide section of the protein is much larger than the functional TGFB1 domain of the protein.
2. The two domains are highly conserved across species and evolutionary pressure
The length of the propeptide is something to consider when we think about the nature of the TGFB1 protein. Its a secreted molecule, that is released from one cell and binds to the membrane receptor of another. Therefore, it would be logical for such a mobile protein to be on the smaller side. The propeptide allows the protein to be translated as a nonfunctional molecule, and also helps the protein be directed and gain its function when it's needed.
The fact that the two domains are highly conserved across species tells us that the various pathways that TGFB1 is involved in are pretty universal. It also provides us with a good idea of how ancient the protein is and how it has changed over time. If you're interested in that aspect of the protein, visit the phylogeny page.
References
[1] Search Allergy Articles. (n.d.). Retrieved April 30, 2017, from https://www.pollen.com/allergy/what-is-allergy
[2] What are protein domains? (2016, July 20). Retrieved April 30, 2017, from https://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[3] (n.d.). Retrieved April 30, 2017, from http://www.proteinstructures.com/Structure/Structure/protein-domains.html
[4] Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
[5] Letunic et al. (2014) Nucleic Acids Res doi: 10.1093/nar/gku949
[2] What are protein domains? (2016, July 20). Retrieved April 30, 2017, from https://www.ebi.ac.uk/training/online/course/introduction-protein-classification-ebi/protein-classification/what-are-protein-domains
[3] (n.d.). Retrieved April 30, 2017, from http://www.proteinstructures.com/Structure/Structure/protein-domains.html
[4] Schultz et al. (1998) Proc. Natl. Acad. Sci. USA 95, 5857-5864
[5] Letunic et al. (2014) Nucleic Acids Res doi: 10.1093/nar/gku949