Sandbox Q123
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| - | <StructureSection load=' | + | <StructureSection load='' size='350' side='right' scene='93/932569/Fn/6' caption='Human glycosylated fibronectin gelatin-binding domain complex with PEG400, dodecaethylene glycol and Zn+2 ions (grey) (PDB code [[3m7p]]) '> |
| - | == | + | == Structural insights == |
| - | + | <scene name='93/932569/Fn/6'>Fibronectin (FN)</scene> is a dimer of homologous monomers linked by S-S bond. Each monomer contains 3 types of repeating units: <scene name='93/932569/Fn_i/2'>FN I</scene>, <scene name='93/932569/Fn_ii/3'>FN II</scene> and <scene name='93/932569/Fn_iii/3'>FN III</scene>. Type I and type II repeats are disulfide-bonded loops, containing about 45 and 60 amino-acids each, while type III repeats are about 90 amino-acids long without S-S bonds<ref name="Pancov">PMID:12244123</ref><ref name="Proctor">PMID:3326130</ref><ref name="Richard">PMID:3916323</ref>. Each module contains several numbered protein binding domains, i.e., the region containing FN I repeat 6, FN II repeat 1-2 and FN I repeat 7-9 is the gelatin binding domain (GBD). | |
| - | == | + | == Biological Functions == |
| - | + | FN is a glycoprotein which binds extracellular matrix components like integrin, collagen, fibrin and others. It plays an important role in cell adhesion, migration and differentiation <ref name="Pancov"/><ref name="Proctor"/>. In addition, FN is also important for the adherence of pathogens to host tissues and the linking between proteins and cells<ref name="Proctor"/><ref name="Mosher">PMID:6326663</ref>. | |
| - | == | + | == Relevance == |
| - | + | FN is associated with inflammation area and the process of wound healing<ref name="Proctor"/><ref name="Mosher"/>. Local treatment of fibronectin has a potential role in accelerating wound closure and the decrease in fibronectin expression can result in poorly healed wound<ref name="Ana">PMID:27554818</ref>. In addition, the level of Fn expression may influence the effectiveness of cancer therapies. Based on the study of head and neck squamous cell carcinoma (HNSCC) cells by Fredrik et al., cells with high level of Fn expression show higher radioresistance compared to those with low level of Fn expression. Therefore, Fn should be considered as a potential marker for radiation resistance<ref name="Fredrik">PMID:20930522</ref>. | |
| - | == | + | == Disease == |
| - | < | + | FN can be divided into soluble and insoluble forms. Soluble FN can be found in plasma and other fluids which circulate in human body. The insoluble form is mainly found on the surface of cells and the extracellular matrix (ECM)<ref name="Pancov"/><ref name="Proctor"/><ref name="Mosher"/>. Although FN can be synthesised by many cell types, soluble (plasma) FN was found to be mainly produced by hepatocytes. Therefore, for patients with liver diseases, the concentration of their plasma FN is lower<ref name="Proctor"/><ref name="Mosher"/>. In addition, Overexpression of Fn1 is associated with lung cancer<ref>PMID:16397245</ref>. |
| - | This is a test, <scene name='93/932569/297-307_space_fill/1'>Space Fill 297-307</scene>, of FN. | ||
== 3D Structures of Fibronectin == | == 3D Structures of Fibronectin == | ||
Current revision
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References
- ↑ 1.0 1.1 1.2 Pankov R, Yamada KM. Fibronectin at a glance. J Cell Sci. 2002 Oct 15;115(Pt 20):3861-3. PMID:12244123
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 Proctor RA. Fibronectin: a brief overview of its structure, function, and physiology. Rev Infect Dis. 1987 Jul-Aug;9 Suppl 4:S317-21. doi:, 10.1093/clinids/9.supplement_4.s317. PMID:3326130 doi:http://dx.doi.org/10.1093/clinids/9.supplement_4.s317
- ↑ Hynes R. Molecular biology of fibronectin. Annu Rev Cell Biol. 1985;1:67-90. doi: 10.1146/annurev.cb.01.110185.000435. PMID:3916323 doi:http://dx.doi.org/10.1146/annurev.cb.01.110185.000435
- ↑ 4.0 4.1 4.2 4.3 Mosher DF. Physiology of fibronectin. Annu Rev Med. 1984;35:561-75. doi: 10.1146/annurev.me.35.020184.003021. PMID:6326663 doi:http://dx.doi.org/10.1146/annurev.me.35.020184.003021
- ↑ Serezani APM, Bozdogan G, Sehra S, Walsh D, Krishnamurthy P, Sierra Potchanant EA, Nalepa G, Goenka S, Turner MJ, Spandau DF, Kaplan MH. IL-4 impairs wound healing potential in the skin by repressing fibronectin expression. J Allergy Clin Immunol. 2017 Jan;139(1):142-151.e5. doi: , 10.1016/j.jaci.2016.07.012. Epub 2016 Aug 20. PMID:27554818 doi:http://dx.doi.org/10.1016/j.jaci.2016.07.012
- ↑ Jerhammar F, Ceder R, Garvin S, Grenman R, Grafstrom RC, Roberg K. Fibronectin 1 is a potential biomarker for radioresistance in head and neck squamous cell carcinoma. Cancer Biol Ther. 2010 Dec 15;10(12):1244-51. doi: 10.4161/cbt.10.12.13432. Epub , 2010 Dec 15. PMID:20930522 doi:http://dx.doi.org/10.4161/cbt.10.12.13432
- ↑ Han S, Khuri FR, Roman J. Fibronectin stimulates non-small cell lung carcinoma cell growth through activation of Akt/mammalian target of rapamycin/S6 kinase and inactivation of LKB1/AMP-activated protein kinase signal pathways. Cancer Res. 2006 Jan 1;66(1):315-23. PMID:16397245 doi:http://dx.doi.org/10.1158/0008-5472.CAN-05-2367
