Editing Fibronectin (section)

== Structure ==
Fibronectin exists as a protein dimer, consisting of two nearly identical [[polypeptide]] chains linked by a pair of [[C-terminal]] [[disulfide bonds]].<ref name="pmid16061370">{{cite journal | vauthors = Mao Y, Schwarzbauer JE | title = Fibronectin fibrillogenesis, a cell-mediated matrix assembly process | journal = Matrix Biology | volume = 24 | issue = 6 | pages = 389–99 | date = Sep 2005 | pmid = 16061370 | doi = 10.1016/j.matbio.2005.06.008 | doi-access =  }}</ref>  Each fibronectin [[Protein subunit|subunit]] has a molecular weight of ~230–~275 kDa<ref>{{Cite web| vauthors = Sitterley G |title=Fibronectin|url=https://www.sigmaaldrich.com/IN/en/technical-documents/technical-article/cell-culture-and-cell-culture-analysis/mammalian-cell-culture/fibronectin#:~:text=Fibronectin%20(FN)%20is%20a%20multifunctional,%20extracellular%20matrix%20glycoprotein%20composed%20of%20two%20nearly%20identical%20disulfide%20bound%20polypeptides%20of%20molecular%20weight%20220%20kDa.|website=Sigma Aldrich}}</ref> and contains multiple copies of three types of [[protein module|modules]]: type I, II, and III.  All three modules are composed of two anti-parallel [[β-sheets]] resulting in a [[Beta-sandwich]]; however, [[Fibronectin type I domain|type I]] and [[Fibronectin type II domain|type II]] are stabilized by intra-chain disulfide bonds, while [[Fibronectin type III domain|type III]] modules do not contain any disulfide bonds. The absence of disulfide bonds in type III modules allows them to partially unfold under applied force.<ref name="pmid12785106">{{cite journal | vauthors = Erickson HP | title = Stretching fibronectin | journal = Journal of Muscle Research and Cell Motility | volume = 23 | issue = 5–6 | pages = 575–80 | year = 2002 | pmid = 12785106 | doi = 10.1023/A:1023427026818 | s2cid = 7052723 }}</ref>

Three regions of variable [[RNA splicing|splicing]] occur along the length of the fibronectin [[Protomer (structural biology)|protomer]].  One or both of the "extra" type III modules (EIIIA and EIIIB) may be present in cellular fibronectin, but they are never present in plasma fibronectin.  A "variable" V-region exists between III<sub>14–15</sub> (the 14th and 15th type III module).  The V-region structure is different from the type I, II, and III modules, and its presence and length may vary.  The V-region contains the binding site for [[α4β1]] integrins.  It is present in most cellular fibronectin, but only one of the two subunits in a plasma fibronectin dimer contains a V-region sequence.

The modules are arranged into several functional and [[protein]]-binding [[protein domain|domains]] along the length of a fibronectin [[monomer]]. There are four fibronectin-binding domains, allowing fibronectin to associate with other fibronectin molecules.<ref name="pmid16061370"/>  One of these fibronectin-binding domains, I<sub>1–5</sub>, is referred to as the "assembly domain", and it is required for the initiation of fibronectin matrix assembly. Modules III<sub>9–10</sub> correspond to the "cell-binding domain" of fibronectin. The [[RGD motif|RGD sequence]] (Arg–Gly–Asp) is located in III<sub>10</sub> and is the site of [[cell adhesion|cell attachment]] via [[α5β1]] and [[αVβ3]] integrins on the cell surface. The "synergy site" is in III<sub>9</sub> and has a role in modulating fibronectin's association with [[α5β1]] [[integrins]].<ref name="pmid9398676">{{cite journal | vauthors = Sechler JL, Corbett SA, Schwarzbauer JE | title = Modulatory roles for integrin activation and the synergy site of fibronectin during matrix assembly | journal = Molecular Biology of the Cell | volume = 8 | issue = 12 | pages = 2563–73 | date = Dec 1997 | pmid = 9398676 | pmc = 25728 | doi = 10.1091/mbc.8.12.2563 }}</ref> Fibronectin also contains domains for [[fibrin]]-binding (I<sub>1–5</sub>, I<sub>10–12</sub>), [[collagen]]-binding (I<sub>6–9</sub>), [[fibulin-1]]-binding (III<sub>13–14</sub>),  [[heparin]]-binding and [[syndecan]]-binding (III<sub>12–14</sub>).<ref name="pmid16061370"/>