Sandbox Q123

Structural insights

is a dimer of homologous monomers linked by S-S bond. Each monomer contains 3 types of repeating units: , and . 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^[1][2][3]. 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 ^[1][2]. In addition, FN is also important for the adherence of pathogens to host tissues and the linking between proteins and cells^[2][4].

Relevance

FN is associated with inflammation area and the process of wound healing^[2][4]. Local treatment of fibronectin has a potential role in accelerating wound closure and the decrease in fibronectin expression can result in poorly healed wound^[5]. 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^[6].

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)^[1][2][4]. 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^[2][4]. In addition, Overexpression of Fn1 is associated with lung cancer^[7].

3D Structures of Fibronectin

Fibronectin 3D structures