Syncytin
From Proteopedia
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| - | + | <StructureSection load='' size='340' side='right' caption='Human syncytin 1 fusion subunit (PDB code [[6ha6]])' scene='90/909935/Syncytin1_1/1'> | |
| - | <StructureSection load='' size='340' side='right' caption=' | + | __TOC__ |
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== Structure == | == Structure == | ||
'''Syncytin''' is a human endogenous envelope protein and is found in the human placenta. There are two forms of syncytin; syncytin 1 and <scene name='90/909935/Syncytin2_1/1'>syncytin 2</scene>, and they are both critical for fetal implantation and placental development. Syncytin 1 contains 538 amino acids and is located on the human chromosome 7 while the specific HERV-W1 coding region is located at 7q21.2. Syncytin has two domains, the surface unit and the transmembrane unit. The surface unit of syncytin 1 is what binds to receptors on the host cell whereas the transmembrane unit supports the fusion of two cells <ref name= 'ncbifrontiers'>Wang, X., Huang, J., & Zhu, F. (2018, September 7). Human endogenous retroviral envelope protein syncytin-1 and inflammatory abnormalities in neuropsychological diseases. Frontiers in psychiatry. Retrieved April 18, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137383/ </ref>. The structure of syncytin is composed of three identical monomers and the precursor that synthesizes the formation is glycosylated gPr73. Once the precursor is cleaved at the surface unit and the transmembrane unit, both units covalently bond via <scene name='90/909935/Syncytin1_3/1'>disulfide binding</scene>. The transmembrane unit is significant as it contains immunosuppressive domain known as the fusion peptide that plays a critical role in the tolerance a mother has to her fetus during pregnancy <ref name= 'fossils'>Durnaoglu, S., Lee, S.-K., & Ahnn, J. (2021). Syncytin, envelope protein of human endogenous retrovirus (Herv): No longer ‘fossil’ in human genome. Animal Cells and Systems, 25(6), 358–368. https://doi.org/10.1080/19768354.2021.2019109 </ref>. Thus, the mother’s immune system does not “attack” the fetus as if it is a foreign body. | '''Syncytin''' is a human endogenous envelope protein and is found in the human placenta. There are two forms of syncytin; syncytin 1 and <scene name='90/909935/Syncytin2_1/1'>syncytin 2</scene>, and they are both critical for fetal implantation and placental development. Syncytin 1 contains 538 amino acids and is located on the human chromosome 7 while the specific HERV-W1 coding region is located at 7q21.2. Syncytin has two domains, the surface unit and the transmembrane unit. The surface unit of syncytin 1 is what binds to receptors on the host cell whereas the transmembrane unit supports the fusion of two cells <ref name= 'ncbifrontiers'>Wang, X., Huang, J., & Zhu, F. (2018, September 7). Human endogenous retroviral envelope protein syncytin-1 and inflammatory abnormalities in neuropsychological diseases. Frontiers in psychiatry. Retrieved April 18, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137383/ </ref>. The structure of syncytin is composed of three identical monomers and the precursor that synthesizes the formation is glycosylated gPr73. Once the precursor is cleaved at the surface unit and the transmembrane unit, both units covalently bond via <scene name='90/909935/Syncytin1_3/1'>disulfide binding</scene>. The transmembrane unit is significant as it contains immunosuppressive domain known as the fusion peptide that plays a critical role in the tolerance a mother has to her fetus during pregnancy <ref name= 'fossils'>Durnaoglu, S., Lee, S.-K., & Ahnn, J. (2021). Syncytin, envelope protein of human endogenous retrovirus (Herv): No longer ‘fossil’ in human genome. Animal Cells and Systems, 25(6), 358–368. https://doi.org/10.1080/19768354.2021.2019109 </ref>. Thus, the mother’s immune system does not “attack” the fetus as if it is a foreign body. | ||
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== Disease == | == Disease == | ||
| - | + | ===Multiple Sclerosis (MS)=== | |
An increase in the expression of Syncytin-1 has been directly correlated to the development of multiple sclerosis. It was also found that syncytin-1 could induce inflammation and was found to cause neurotoxic cascades as well. This neurotoxic cascade includes the secretion of proinflammatory cytokines. Multiple sclerosis is an inflammatory disorder that causes the demyelination of axons. It was found that overexpression of Syncytin-1 can cause tissue damage and demyelination if affecting glial cells. Overexpression of Syncytin-1 in immune cells that are activated in multiple sclerosis and patients that are affected with acute infections have an elevated level of monocytes that contain the protein. Along with this, after interaction with lipopolysaccharides, the level of syncytin-1 also increased in T and B lymphocytes along with natural killer cells which implies that syncytin-1 may have a role in immune cell activation in the early stages and may even be involved in the pathogenesis of multiple sclerosis <ref name='ncbifrontiers'/>. | An increase in the expression of Syncytin-1 has been directly correlated to the development of multiple sclerosis. It was also found that syncytin-1 could induce inflammation and was found to cause neurotoxic cascades as well. This neurotoxic cascade includes the secretion of proinflammatory cytokines. Multiple sclerosis is an inflammatory disorder that causes the demyelination of axons. It was found that overexpression of Syncytin-1 can cause tissue damage and demyelination if affecting glial cells. Overexpression of Syncytin-1 in immune cells that are activated in multiple sclerosis and patients that are affected with acute infections have an elevated level of monocytes that contain the protein. Along with this, after interaction with lipopolysaccharides, the level of syncytin-1 also increased in T and B lymphocytes along with natural killer cells which implies that syncytin-1 may have a role in immune cell activation in the early stages and may even be involved in the pathogenesis of multiple sclerosis <ref name='ncbifrontiers'/>. | ||
| - | + | ===Schizophrenia=== | |
The overexpression of Syncytin-1 has also been loosely correlated to disorders such as schizophrenia. Brain-derived neurotrophic factors, neurotrophic tyrosine kinase receptor types, and dopamine receptor D3 are all significant in the development of schizophrenia, and it was found that the overexpression of the protein in human U251 glioma cells correlates to the increase of these receptors <ref name='fossils'/>. Studies have shown that an increase in the transcription of syncytin-1 is also correlated to the development of schizophrenia. However, several studies have also shown that there is no significant difference in the expression level of syncytin-1 in the development of schizophrenia <ref name='ncbifrontiers'/>. However, these findings imply that syncytin may have a variety of different ways of affecting the development of schizophrenia. | The overexpression of Syncytin-1 has also been loosely correlated to disorders such as schizophrenia. Brain-derived neurotrophic factors, neurotrophic tyrosine kinase receptor types, and dopamine receptor D3 are all significant in the development of schizophrenia, and it was found that the overexpression of the protein in human U251 glioma cells correlates to the increase of these receptors <ref name='fossils'/>. Studies have shown that an increase in the transcription of syncytin-1 is also correlated to the development of schizophrenia. However, several studies have also shown that there is no significant difference in the expression level of syncytin-1 in the development of schizophrenia <ref name='ncbifrontiers'/>. However, these findings imply that syncytin may have a variety of different ways of affecting the development of schizophrenia. | ||
| - | + | ===Alzheimer's Disease=== | |
An abnormal influx of calcium has been linked to the development of Alzheimer’s Disease in individuals. Overexpression of syncytin-1 has been linked to the influx of calcium ions in neuroblastoma cells. Along with the influx of calcium, nitric oxide also contributes to the development of Alzheimer’s Disease as it regulates the inflammatory response of the brain and neuronal cells <ref name='fossils'/>. An increase in syncytin-1 levels has the capability to activate the enzyme [[Nitric Oxide Synthase]] in astrocytes which then induces the release of the redox reaction product, nitric oxide. These, in turn, are cytotoxic to oligodendrocytes which can damage axons <ref name='ncbifrontiers'/>. | An abnormal influx of calcium has been linked to the development of Alzheimer’s Disease in individuals. Overexpression of syncytin-1 has been linked to the influx of calcium ions in neuroblastoma cells. Along with the influx of calcium, nitric oxide also contributes to the development of Alzheimer’s Disease as it regulates the inflammatory response of the brain and neuronal cells <ref name='fossils'/>. An increase in syncytin-1 levels has the capability to activate the enzyme [[Nitric Oxide Synthase]] in astrocytes which then induces the release of the redox reaction product, nitric oxide. These, in turn, are cytotoxic to oligodendrocytes which can damage axons <ref name='ncbifrontiers'/>. | ||
| - | + | ===Cancer=== | |
Syncytin-1 has been correlated to several different kinds of cancers including breast cancer, carcinomas, and endometrial cancers. As mentioned above, the env gene of syncytin-1 can become activated and promote the production of cancerous cells <ref name='fossils'/>. Overexpression in syncytin-1 contributes to increased proliferation, metastasis, and the growth of tumors in individuals due to the methylation of DNA and the 5’LTR of the syncytin gene. The overmethylation contributes to the silencing of the tumor-suppressing gene <ref name= 'cancer'>Locke, W. J., Guanzon, D., Ma, C., Liew, Y. J., Duesing, K. R., Fung, K. Y. C., & Ross, J. P. (2019, November 14). DNA methylation cancer biomarkers: Translation to the clinic. Frontiers. Retrieved April 27, 2022, from https://www.frontiersin.org/articles/10.3389/fgene.2019.01150/full#:~:text=Hypermethylation%20can%20drive%20the%20silencing,et%20al.%2C%202015). </ref>. As a result, if both tumor suppressor genes in a cell contain a mutation, then the suppressor gene is deactivated. With the tumor suppressor gene losing function, cells may grow and divide unregulated, resulting in cancer. | Syncytin-1 has been correlated to several different kinds of cancers including breast cancer, carcinomas, and endometrial cancers. As mentioned above, the env gene of syncytin-1 can become activated and promote the production of cancerous cells <ref name='fossils'/>. Overexpression in syncytin-1 contributes to increased proliferation, metastasis, and the growth of tumors in individuals due to the methylation of DNA and the 5’LTR of the syncytin gene. The overmethylation contributes to the silencing of the tumor-suppressing gene <ref name= 'cancer'>Locke, W. J., Guanzon, D., Ma, C., Liew, Y. J., Duesing, K. R., Fung, K. Y. C., & Ross, J. P. (2019, November 14). DNA methylation cancer biomarkers: Translation to the clinic. Frontiers. Retrieved April 27, 2022, from https://www.frontiersin.org/articles/10.3389/fgene.2019.01150/full#:~:text=Hypermethylation%20can%20drive%20the%20silencing,et%20al.%2C%202015). </ref>. As a result, if both tumor suppressor genes in a cell contain a mutation, then the suppressor gene is deactivated. With the tumor suppressor gene losing function, cells may grow and divide unregulated, resulting in cancer. | ||
| + | == Syncytiin 3D structures== | ||
| + | |||
| + | [[5ha6]], [[6rx1]] – hSct1 fusion subunit 343-435 – human<br /> | ||
| + | [[1y4m]], [[6rx3]] – hSct2 fusion subunit 375-468 <br /> | ||
| + | [[7oix]] – hSct2 + MFSD2A – Cryo EM<br /> | ||
</StructureSection> | </StructureSection> | ||
== References == | == References == | ||
<references/> | <references/> | ||
| + | [[Category:Topic Page]] | ||
Current revision
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References
- ↑ 1.0 1.1 1.2 1.3 1.4 Wang, X., Huang, J., & Zhu, F. (2018, September 7). Human endogenous retroviral envelope protein syncytin-1 and inflammatory abnormalities in neuropsychological diseases. Frontiers in psychiatry. Retrieved April 18, 2022, from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137383/
- ↑ 2.0 2.1 2.2 2.3 2.4 Durnaoglu, S., Lee, S.-K., & Ahnn, J. (2021). Syncytin, envelope protein of human endogenous retrovirus (Herv): No longer ‘fossil’ in human genome. Animal Cells and Systems, 25(6), 358–368. https://doi.org/10.1080/19768354.2021.2019109
- ↑ Ruigrok, K., Vaney, M.-C., Buchrieser, J., Baquero, E., Hellert, J., Baron, B., England, P., Schwartz, O., Rey, F. A., & Backovic, M. (2019, November 8). X-ray structures of the post-fusion 6-helix bundle of the human Syncytins and their functional implications. Journal of Molecular Biology. Retrieved April 18, 2022, from https://www.sciencedirect.com/science/article/pii/S0022283619306163
- ↑ Cáceres, M., & Thomas, J. W. (2006). The gene of retroviral origin syncytin 1 is specific to hominoids and is inactive in Old World Monkeys. Journal of Heredity, 97(2), 100–106. https://doi.org/10.1093/jhered/esj011
- ↑ Locke, W. J., Guanzon, D., Ma, C., Liew, Y. J., Duesing, K. R., Fung, K. Y. C., & Ross, J. P. (2019, November 14). DNA methylation cancer biomarkers: Translation to the clinic. Frontiers. Retrieved April 27, 2022, from https://www.frontiersin.org/articles/10.3389/fgene.2019.01150/full#:~:text=Hypermethylation%20can%20drive%20the%20silencing,et%20al.%2C%202015).
