User:Kristen Williams/sandbox 1
From Proteopedia
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The Ependymin protein has been found in many different living organisms. Human ependymin protein can be found in the PDB under 6JLD. There are a few variations of this protein that have been found that fall into the ependymin family of proteins. These proteins were originally known as fish-specific glycoproteins<ref name="Dougal">McDougall, C., Hammond, M.J., Dailey, S.C. et al. The evolution of ependymin-related proteins. BMC Evol Biol 18, 182 (2018). https://doi.org/10.1186/s12862-018-1306-y</ref>. Fish ependymin proteins involve the central nervous system and can include plasticity and memory<ref name="Dougal"/>. For a long time, these proteins were thought to be specific to fish until the recent discovery of many different ependymin proteins that have been found in mammals<ref name="Dougal"/>. The ependymin family became much larger after this discovery<ref name="Dougal"/>. They have more recently been discovered in humans and other animals. The exact function of the Ependymin protein is unknown, however many correlations have been studied regarding the nervous system. The ependymin family became divided into four groups after a genome duplication<ref name="Suarez"/>. These four groups were decided and grouped by their amino acid sequence: 1) brain-specific sequenced proteins unique to teleost fishes and the first known ependymin protein; 2) non-brain specific proteins found in fishes; 3) a family that is not specific to any tissue and found only in deuterostomes; and 4) a unique family that is widely expressed and is found in protostomes deuterostomes and invertebrates<ref name="Suarez">Suárez-Castillo, E. C., & García-Arrarás, J. E. (2007). Molecular evolution of the ependymin protein family: a necessary update. BMC evolutionary biology, 7, 23. https://doi.org/10.1186/1471-2148-7-23</ref>. This protein has a wide array of functions that are dependent on amino acid formation. This very diverse family of proteins has been widely researched for many years. | The Ependymin protein has been found in many different living organisms. Human ependymin protein can be found in the PDB under 6JLD. There are a few variations of this protein that have been found that fall into the ependymin family of proteins. These proteins were originally known as fish-specific glycoproteins<ref name="Dougal">McDougall, C., Hammond, M.J., Dailey, S.C. et al. The evolution of ependymin-related proteins. BMC Evol Biol 18, 182 (2018). https://doi.org/10.1186/s12862-018-1306-y</ref>. Fish ependymin proteins involve the central nervous system and can include plasticity and memory<ref name="Dougal"/>. For a long time, these proteins were thought to be specific to fish until the recent discovery of many different ependymin proteins that have been found in mammals<ref name="Dougal"/>. The ependymin family became much larger after this discovery<ref name="Dougal"/>. They have more recently been discovered in humans and other animals. The exact function of the Ependymin protein is unknown, however many correlations have been studied regarding the nervous system. The ependymin family became divided into four groups after a genome duplication<ref name="Suarez"/>. These four groups were decided and grouped by their amino acid sequence: 1) brain-specific sequenced proteins unique to teleost fishes and the first known ependymin protein; 2) non-brain specific proteins found in fishes; 3) a family that is not specific to any tissue and found only in deuterostomes; and 4) a unique family that is widely expressed and is found in protostomes deuterostomes and invertebrates<ref name="Suarez">Suárez-Castillo, E. C., & García-Arrarás, J. E. (2007). Molecular evolution of the ependymin protein family: a necessary update. BMC evolutionary biology, 7, 23. https://doi.org/10.1186/1471-2148-7-23</ref>. This protein has a wide array of functions that are dependent on amino acid formation. This very diverse family of proteins has been widely researched for many years. | ||
| - | Human ependymin protein has been shown to be correlated with a few diseases such as Dupuytren’s disease of the plantar fascia and glaucoma | + | Human ependymin protein has been shown to be correlated with a few diseases such as Dupuytren’s disease of the plantar fascia and glaucoma<ref name="Wei"> Wei, Y., Xiong, Z.J., Li, J. et al. Crystal structures of human lysosomal EPDR1 reveal homology with the superfamily of bacterial lipoprotein transporters. Commun Biol 2, 52 (2019). https://doi.org/10.1038/s42003-018-0262-9</ref>. These linkages unfortunately have not given a clear look into the function of this protein<ref name="Wei"/>. |
== Location == | == Location == | ||
| - | Fish ependymin protein is present in the extracellular fluid in the brain of fish with an unknown exact function<ref name="Park">Park, J. K., Kim, K. Y., Sim, Y. W., Kim, Y. I., Kim, J. K., Lee, C., Han, J., Kim, C. U., Lee, J. E., & Park, S. (2019). Structures of three ependymin-related proteins suggest their function as a hydrophobic molecule binder. IUCrJ, 6(Pt 4), 729–739. https://doi.org/10.1107/S2052252519007668</ref>. The human ependymin protein, however, has been found as a lysosomal protein<ref name="Park"/>. All ependymin proteins have showed endoplasmic reticulum targeting signals in their amino acid sequences, however, on human ependymin proteins a mannose-6-phosphate tag was located as well<ref name="Park"/>. This mannose-6-phosphate tag resembles a protein that is folded in the endoplasmic reticulum and sent to the Golgi apparatus for further modification in which the M6P tag will send it off to the lysosome<ref name="Park"/>. Lysosomal proteins are fairly well known, and many have known functions, however few lysosomal proteins are classified by their location alone | + | Fish ependymin protein is present in the extracellular fluid in the brain of fish with an unknown exact function<ref name="Park">Park, J. K., Kim, K. Y., Sim, Y. W., Kim, Y. I., Kim, J. K., Lee, C., Han, J., Kim, C. U., Lee, J. E., & Park, S. (2019). Structures of three ependymin-related proteins suggest their function as a hydrophobic molecule binder. IUCrJ, 6(Pt 4), 729–739. https://doi.org/10.1107/S2052252519007668</ref>. The human ependymin protein, however, has been found as a lysosomal protein<ref name="Park"/>. All ependymin proteins have showed endoplasmic reticulum targeting signals in their amino acid sequences, however, on human ependymin proteins a mannose-6-phosphate tag was located as well<ref name="Park"/>. This mannose-6-phosphate tag resembles a protein that is folded in the endoplasmic reticulum and sent to the Golgi apparatus for further modification in which the M6P tag will send it off to the lysosome<ref name="Park"/>. Lysosomal proteins are fairly well known, and many have known functions, however few lysosomal proteins are classified by their location alone<ref name="Wei"/>. Ependymin proteins are unique in the way that no other known protein seems to have similar amino acid sequences which is why it is so important that the function of this protein should be known<ref name="Park"/>. |
== Structure == | == Structure == | ||
| - | Consisting of about 200 amino acids, ependymins are considered a secreted glycoprotein<ref name="Dougal"/>. Ependymin consists of three disulfide linkages joining together an alpha and beta polypeptide chain | + | Consisting of about 200 amino acids, ependymins are considered a secreted glycoprotein<ref name="Dougal"/>. Ependymin consists of three disulfide linkages joining together an alpha and beta polypeptide chain<ref name="Shas"> PMID: 1831964</ref>. This protein is very unique and is does not contain any long sequences similar to any known polypeptides<ref name="Shas"/>. However, after a closer look, there are a few short amino acid sequences that contain similarities to tubulin, fibronectin, and laminin<ref name="Shas"/>. All human ependymin proteins contain two β-sheets that are stacked on top of each other<ref name="Park"/>. These two sheets have a unique curve to them allowing for a deep hydrophobic region to be present on the molecule<ref name="Park"/>. This β sheet structure that contains a curvature has previously only been found in bacteria<ref name="Wei"/>. This includes two segments, one being strands 1-6 and the next being strands 7-11<ref name="Wei"/>. The β6 and β7 are at opposite ends and exhibit hydrogen bonding with β1 and β11 respectively<ref name="Wei"/>. The three disulfide linkages located on this molecule join together six cysteine residues<ref name="Park"/>. All ependymin related proteins have been shown to have anywhere from four to six cysteine residues<ref name="Park"/>. |
<table> | <table> | ||
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| - | The linkages of these cysteine residues are respectively: Cys42 and Cys172, Cys88 and Cys222, and Cys113 and Cys210 as shown above | + | The linkages of these cysteine residues are respectively: Cys42 and Cys172, Cys88 and Cys222, and Cys113 and Cys210 as shown above<ref name="Wei"/>. The two chains of this protein are attached through hydrophilic contact<ref name="Wei"/>. The one cysteine residue that is found only in vertebrates is the Cys88 and Cys222 linkage<ref name="Wei"/>. Human ependymin has been shown to be structurally similar to LolA and LolB proteins<ref name="Wei"/>. These similarities include a deep groove for ligand binding, non-traditional N and C terminus, disulfide linkages throughout the chain, and glycosylated elements<ref name="Wei"/>. The folding of the LolA and LolB proteins has been shown to be similar in ependymins; this is important because this has previously only been associated with bacteria<ref name="Wei"/>. We now have more knowledge about eukaryotes and archaea as well through the discovery of the structure of ependymins<ref name="Wei"/>. This protein is unique in that it has two lipid binding grooves the flat region of the homodimer which can be assumed to aid in membrane binding to give a larger contact surface for use in lipid transport<ref name="Wei"/>. As stated previously, research suggests that human ependymin could potentially be a lysosomal protein in which it can undergo lipid catabolism<ref name="Wei"/>. Research suggests that ependymin is not likely to function as an enzyme or be used structurally but more likely to be considered a transporter or activator protein based on its known qualities<ref name="Wei"/>. The evidence obtained does not give conclusive results as per the function of ependymins, however they remain consistent with previous findings<ref name="Wei"/>. |
Another unique characteristic of human ependymin protein is that it contains a calcium binding site along with two asparagine residues that are glycosylated<ref name="Park"/>. Fish ependymin related proteins still have an unknown function due to lack of knowledge about the protein, however human ependymin protein is slowly being uncovered and the calcium binding sites indicate that this protein could potentially be a secreted protein<ref name="Park"/>. All of these known facts about ependymin related proteins puts us one step closer to understanding how this protein works. | Another unique characteristic of human ependymin protein is that it contains a calcium binding site along with two asparagine residues that are glycosylated<ref name="Park"/>. Fish ependymin related proteins still have an unknown function due to lack of knowledge about the protein, however human ependymin protein is slowly being uncovered and the calcium binding sites indicate that this protein could potentially be a secreted protein<ref name="Park"/>. All of these known facts about ependymin related proteins puts us one step closer to understanding how this protein works. | ||
== Research Findings on Fish Ependymins == | == Research Findings on Fish Ependymins == | ||
| - | Research on this protein is very important and can help lead us to a known function of ependymin protein. Looking at the ependymin protein alone does not give clear answers. However, when looking at what happens at a synapse during memory formation, we can gain a bigger picture idea of the role of ependymins. The changes that happen to the fibrous insoluble polymers present in the brain of goldfish give rise to the role of ependymins during memory formation | + | Research on this protein is very important and can help lead us to a known function of ependymin protein. Looking at the ependymin protein alone does not give clear answers. However, when looking at what happens at a synapse during memory formation, we can gain a bigger picture idea of the role of ependymins. The changes that happen to the fibrous insoluble polymers present in the brain of goldfish give rise to the role of ependymins during memory formation<ref name="Shas"/>. These polymers can be polymerized by the fish ependymin protein in the presence of low calcium in the brain<ref name="Shas"/>. These biochemical changes were indicative of synaptic changes as well when studying memory formation<ref name="Shas"/>. This does not give a clear answer on the function of ependymin proteins; however, it gives more insight into a potential function and role in the brain of goldfish during memory formation. |
Another research study highlighted the role of ependymins in memory formation also through a study with goldfish. He used similar techniques when observing the ependymin protein, but he looked at the concentration of ependymin protein in the brain. In the goldfish that succeeded in their training, ependymin protein increased by about forty percent when compared to those who had not completed any training<ref name="Schmidt"> PMID: 3572403</ref>. An unusual finding was that shortly after the fish had finished training the levels of ependymin in their brains had decreased prominently before skyrocketing to almost one hundred and forty percent about 10 hours after training<ref name="Schmidt"/>. A general statement can be made about these findings; during memory formation he had found that ependymin proteins had been used to execute molecular reactions<ref name="Schmidt"/>. The drop in ependymin protein could have been explained by low concentrations of the protein triggering more of the proteins to be made and excreted into the extracellular fluid in the brain<ref name="Schmidt"/>. | Another research study highlighted the role of ependymins in memory formation also through a study with goldfish. He used similar techniques when observing the ependymin protein, but he looked at the concentration of ependymin protein in the brain. In the goldfish that succeeded in their training, ependymin protein increased by about forty percent when compared to those who had not completed any training<ref name="Schmidt"> PMID: 3572403</ref>. An unusual finding was that shortly after the fish had finished training the levels of ependymin in their brains had decreased prominently before skyrocketing to almost one hundred and forty percent about 10 hours after training<ref name="Schmidt"/>. A general statement can be made about these findings; during memory formation he had found that ependymin proteins had been used to execute molecular reactions<ref name="Schmidt"/>. The drop in ependymin protein could have been explained by low concentrations of the protein triggering more of the proteins to be made and excreted into the extracellular fluid in the brain<ref name="Schmidt"/>. | ||
Revision as of 21:10, 10 April 2021
Ependymin Proteins
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References
- ↑ 1.0 1.1 1.2 1.3 1.4 McDougall, C., Hammond, M.J., Dailey, S.C. et al. The evolution of ependymin-related proteins. BMC Evol Biol 18, 182 (2018). https://doi.org/10.1186/s12862-018-1306-y
- ↑ 2.0 2.1 Suárez-Castillo, E. C., & García-Arrarás, J. E. (2007). Molecular evolution of the ependymin protein family: a necessary update. BMC evolutionary biology, 7, 23. https://doi.org/10.1186/1471-2148-7-23
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 Wei, Y., Xiong, Z.J., Li, J. et al. Crystal structures of human lysosomal EPDR1 reveal homology with the superfamily of bacterial lipoprotein transporters. Commun Biol 2, 52 (2019). https://doi.org/10.1038/s42003-018-0262-9
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 Park, J. K., Kim, K. Y., Sim, Y. W., Kim, Y. I., Kim, J. K., Lee, C., Han, J., Kim, C. U., Lee, J. E., & Park, S. (2019). Structures of three ependymin-related proteins suggest their function as a hydrophobic molecule binder. IUCrJ, 6(Pt 4), 729–739. https://doi.org/10.1107/S2052252519007668
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 Shashoua VE. Ependymin, a brain extracellular glycoprotein, and CNS plasticity. Ann N Y Acad Sci. 1991;627:94-114. doi: 10.1111/j.1749-6632.1991.tb25916.x. PMID:1831964 doi:http://dx.doi.org/10.1111/j.1749-6632.1991.tb25916.x
- ↑ 6.0 6.1 6.2 6.3 Schmidt R. Changes in subcellular distribution of ependymins in goldfish brain induced by learning. J Neurochem. 1987 Jun;48(6):1870-8. doi: 10.1111/j.1471-4159.1987.tb05750.x. PMID:3572403 doi:http://dx.doi.org/10.1111/j.1471-4159.1987.tb05750.x
