Fibronectin functional domains

Ghosh K, Ren X-D, Shu XZ, Prestwich GD, Clark RAF. Fibronectin functional domains coupled to hyaluronan stimulate adult human dermal fibroblast responses critical for wound healing. Tissue Eng 2006 12 601-613. 

Figure 48-3. Schematic representation of fibronectin. Seven functional domains of fibronectin are represented two different types of domain for heparin, cell-binding, and fibrin are shown. The domains are composed of various combinations of three structural motifs (I, II, and III), not depicted in the figure. Also not shown is the fact that fibronectin is a dimer joined by disulfide bridges near the carboxyl terminals of the monomers. The approximate location of the RGD sequence of fibronectin, which interacts with a variety of fibronectin integrin receptors on cell surfaces, is indicated by the arrow. (Redrawn after Yamada KM Adhesive recognition sequences.

After catalytic domains, the next most common domains are CBDs which are usually j oined to the catalytic domain by a short tinker peptide. Cellulases that are present in cellulosomes contain short domains called dockerins that bind to specific sites on a scaffoldin protein to form a cellulosome [30]. A number of cellulases contain fibronectin-like domains, but the function of these domains is not known [6]. There are several other domains with unknown functions [6]. 

Schematic representation of a fibronectin molecule. It is a dimer of similar subunits (M.W. of each 250,000) joined by a pair of disulfide linkages. The various functional domains by which fibronectin can interact with other protein and membrane components are indicated.

Similarly, Panitch et al. have incorporated periodically spaced fibronectin CS5 domains into ELPs (60). These polymers are intended to function as surfaces for vascular grafts and enhance the attachment of endothelial cells to a glass substrate. 

Fibronectin is an adhesion protein like laminin, vitronectin, and von Wille-brand factor, which are synthesized by the cells themselves to build up the ECM. The glycoprotein fibronectin with a molecular weight between 220,000 and 250,000 consists of two similar subunits, which are connected close to their C-terminus by disulfide bridges. The subunits are composed of functional domains [121]. The cell binding domain with the characteristic sequence Gly-Arg-Gly-Asp-Ser (GRGDS) is of special interest [122]. Models of the subunit of the fibronectin molecule and its cell binding domain are presented in Fig. 21. 

The formation of fibronectin fibrils, another relatively well-studied supramolecular structure of ECM polymers, was extensively studied in vitro as well. Many different cell types synthesize fibronectin and secrete it as a disulfide-bonded dimer composed of 230-270 kDa subunits. Each subunit contains three types of repeating modules, types I, II, and III. These modules comprise functional domains that mediate interactions with other ECM components, with cell surface receptors and with fibronectin itself. Fibronectin matrix assembly involves binding domains and repeating modules from all regions of fibronectin which participate in interactions with cell surface receptors and with other fibronectin molecules. Newly secreted fi-... 

FIGURE 7-1 The immunoglobulin (Ig) gene family of molecules. Several varieties of Ig domain-containing molecules are contained within the Ig gene superfamily. Most are type I membrane proteins some have only Ig domains or other moieties that may convey function (see text). V, variable Ig domain C, constant Ig domain MAG, myelin-associated glycoprotein NCAM, neural cell adhesion molecule GPI, glycosylphosphatidyl-inositol EC, extracellular domain FN, fibronectin. 

Because of the complexity of its function in the biological environment, fibronectin has been shown to have selected areas or domains along its chain which can be associated to specific binding functions. For example, as shown in Figure 8.11, there are at least two domains with direct cellular binding activity, another domain binds... 

The MMPs are a family of zinc-dependent neutral endopep-tidases that share structural domains but differ in substrate specificity, cellular sources, and inductivity (Table I). All the MMPs are important for remodeling of the extra cellular matrix and share the following functional features (/) they degrade extracellular matrix components, including fibronectin, collagen, elastin, proteoglycans, and laminin, (//) they are secreted in a latent proform and require activation for proteolytic activity, (///) they contain zinc at their active site and need calcium for stability, (/V) they function at neutral pH, and (v) they are inhibited by specific tissue inhibitors of metalloproteinases (TIMPs). 

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