Sandbox Reserved 1591
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{{Sandbox_Reserved_JMeans}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | {{Sandbox_Reserved_JMeans}}<!-- PLEASE ADD YOUR CONTENT BELOW HERE --> | ||
| - | == | + | ==Human Folate Receptor== |
| - | <StructureSection load='4LRH' size='340' side='right' caption='Human Folate Receptor' scene=''> | + | <StructureSection load='4LRH' size='340' side='right' caption='α Human Folate Receptor' scene=''> |
This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | This is a default text for your page ''''''. Click above on '''edit this page''' to modify. Be careful with the < and > signs. | ||
You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref name="Chen">PMID: 23851396</ref> to the rescue. | You may include any references to papers as in: the use of JSmol in Proteopedia <ref>DOI 10.1002/ijch.201300024</ref> or to the article describing Jmol <ref name="Chen">PMID: 23851396</ref> to the rescue. | ||
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== Function == | == Function == | ||
Folates are one-carbon donors for the synthesis of purines and thymidine, which are both essential components of nucleic acids <ref name="Wibowo"/>. This means that they are indirectly used for the methylation of DNA, proteins, and lipids<ref name="Wibowo"/>. The three subtypes of folate receptors that were previously mentioned (FR-alpha, FR-beta, FR-gamma) also play a role in other happenings in the human body. They mediated folate uptake in cells through endocytosis<ref name="Wibowo"/>. The endosome's acidic environment promotes the release of these folate receptors, which is then transported into the cell's cytoplasm by a proton-coupled folate transporter<ref name="Wibowo"/>. Expression of the folate cells however, is restricted to cells that are important for embryonic development which do include the placental and neural tubes, among other things<ref name="Wibowo"/>. In the human body, FR-alpha is the most widely expressed but is still low in normal tissues with higher levels of expression in many rapidly dividing tumors<ref name="Wibowo"/>. Folate receptors also have gene encoding functions. Human folate receptor-alpha has been implicated in folate transcytosis in the kidney and delivery into the central nervous system<ref name="Wibowo"/>. Human folate receptors beta and gamma gene encoding functions are unclear when expressed normally except is is known that the beta subtype is capable of delivering folate and folate-derived molecules into activated macrophages or certain leukemic cells<ref name="Wibowo"/>. | Folates are one-carbon donors for the synthesis of purines and thymidine, which are both essential components of nucleic acids <ref name="Wibowo"/>. This means that they are indirectly used for the methylation of DNA, proteins, and lipids<ref name="Wibowo"/>. The three subtypes of folate receptors that were previously mentioned (FR-alpha, FR-beta, FR-gamma) also play a role in other happenings in the human body. They mediated folate uptake in cells through endocytosis<ref name="Wibowo"/>. The endosome's acidic environment promotes the release of these folate receptors, which is then transported into the cell's cytoplasm by a proton-coupled folate transporter<ref name="Wibowo"/>. Expression of the folate cells however, is restricted to cells that are important for embryonic development which do include the placental and neural tubes, among other things<ref name="Wibowo"/>. In the human body, FR-alpha is the most widely expressed but is still low in normal tissues with higher levels of expression in many rapidly dividing tumors<ref name="Wibowo"/>. Folate receptors also have gene encoding functions. Human folate receptor-alpha has been implicated in folate transcytosis in the kidney and delivery into the central nervous system<ref name="Wibowo"/>. Human folate receptors beta and gamma gene encoding functions are unclear when expressed normally except is is known that the beta subtype is capable of delivering folate and folate-derived molecules into activated macrophages or certain leukemic cells<ref name="Wibowo"/>. | ||
| - | == | + | == Applications == |
| - | + | Many cancers highly express the alpha folate receptor, therefore resulting in becoming an important target for receptor-mediated chemotherapy <ref name="Wibowo"/>. Folate receptor targeted therapies are expected to be effective in treatment of many types of cancers and inflammatory diseases<ref name="Cancer">PMID: 23934049</ref>. Alpha folate receptors are overexpressed in nonmucinous adenocarcinomas of the ovary, uterus, breast, cervix, kidney, and colon <ref name="Cancer"/>. Beta human folate receptors expression is increased in certain leukemias, its also increased in cells that are involved in the pathogenesis of rheumatoid arthritis and other conditions such as psoriasis and Crohn's disease<ref name="Cancer"/>. | |
== Structural highlights == | == Structural highlights == | ||
| - | <scene name='82/824636/N-glycosylation_sites/1'>N-glycosylation sites</scene> | + | The structure of the alpha folate receptor is composed of <scene name='82/824636/Folic_acid_and_receptor/1'>folic acid (pink) and the receptor (green)</scene>. The structure of FRα contains a long and open folate binding pocket. Folic acid is oriented with its basic pteroate moiety docked deep inside the negatively charged pocket and the two negatively charged carboxyl groups<ref name="Chen"/>. |
| + | |||
| + | The folate receptor is a glycoprotein which binds the vitamin folic acid and its analogues. Alpha folate receptors have three predicted <scene name='82/824636/N-glycosylation_sites/1'>N-glycosylation sites</scene> (N47, N139, and N179)<ref name="Structure">PMID: 9515058</ref>. Glycosylation is a structural feature of all three isoforms of the human folate receptor <ref name="Structure"/>. At least on of the core glycosylated residues is necessary for the synthesis of FRα in its active conformation <ref name="Structure"/>. | ||
This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes. | ||
Current revision
| This Sandbox is Reserved from September 14, 2021, through May 31, 2022, for use in the class Introduction to Biochemistry taught by User:John Means at the University of Rio Grande, Rio Grande, OH, USA. This reservation includes 5 reserved sandboxes (Sandbox Reserved 1590 through Sandbox Reserved 1594). |
To get started:
More help: Help:Editing. For an example of a student Proteopedia page, please see Photosystem II, Tetanospasmin, or Guanine riboswitch. |
Human Folate Receptor
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References
- ↑ Hanson, R. M., Prilusky, J., Renjian, Z., Nakane, T. and Sussman, J. L. (2013), JSmol and the Next-Generation Web-Based Representation of 3D Molecular Structure as Applied to Proteopedia. Isr. J. Chem., 53:207-216. doi:http://dx.doi.org/10.1002/ijch.201300024
- ↑ 2.0 2.1 2.2 2.3 Chen C, Ke J, Zhou XE, Yi W, Brunzelle JS, Li J, Yong EL, Xu HE, Melcher K. Structural basis for molecular recognition of folic acid by folate receptors. Nature. 2013 Jul 14. doi: 10.1038/nature12327. PMID:23851396 doi:10.1038/nature12327
- ↑ 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 Wibowo AS, Singh M, Reeder KM, Carter JJ, Kovach AR, Meng W, Ratnam M, Zhang F, Dann CE 3rd. Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition. Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):15180-8. doi:, 10.1073/pnas.1308827110. Epub 2013 Aug 9. PMID:23934049 doi:10.1073/pnas.1308827110
- ↑ 4.0 4.1 4.2 Wibowo AS, Singh M, Reeder KM, Carter JJ, Kovach AR, Meng W, Ratnam M, Zhang F, Dann CE 3rd. Structures of human folate receptors reveal biological trafficking states and diversity in folate and antifolate recognition. Proc Natl Acad Sci U S A. 2013 Sep 17;110(38):15180-8. doi:, 10.1073/pnas.1308827110. Epub 2013 Aug 9. PMID:23934049 doi:10.1073/pnas.1308827110
- ↑ 5.0 5.1 5.2 Roberts SJ, Petropavlovskaja M, Chung KN, Knight CB, Elwood PC. Role of individual N-linked glycosylation sites in the function and intracellular transport of the human alpha folate receptor. Arch Biochem Biophys. 1998 Mar 15;351(2):227-35. doi: 10.1006/abbi.1997.0551. PMID:9515058 doi:http://dx.doi.org/10.1006/abbi.1997.0551
