InterPro domain: IPR003961

Fibronectin is a dimeric glycoprotein composed of disulfide-linked subunitswith a molecular weight of 220-250kDa each. It is involved in cell adhesion,cell morphology, thrombosis, cell migration, and embryonic differentiation. Fibronectin is a modular protein composed of homologous repeats of threeprototypical types of domains known as types I, II, and III [ 1 ].

Fibronectin type-III (FN3) repeats are both the largest and the most common of the fibronectin subdomains. Domains homologous to FN3 repeats have been foundin various animal protein families including other extracellular-matrixmolecules, cell-surface receptors, enzymes, and muscle proteins [ 2 ]. Structures of individual FN3 domains have revealed a conserved beta sandwich fold with one beta sheet containing four strands and the other sheet containing three strands (see for example {PDB:1TEN}) [ 3 ]. This fold is topologically very similar to that of Ig-like domains, with a notable difference being the lack of a conserved disulfide bond in FN3 domains. Distinctive hydrophobic core packing and the lack of detectablesequence homology between immunoglobulin and FN3 domains suggest, however,that these domains are not evolutionarily related [ 4 ].

FN3 exhibits functional as well as structural modularity. Sites of interaction with other molecules have been mapped to short stretch of amino acids such as the Arg-Gly-Asp (RGD) sequence found in various FN3 domains. The RGD sequences is involved in interactions with integrin. Small peptides containing the RGD sequence can modulate a variety of cell adhesion invents associated with thrombosis, inflammation, and tumor metastasis. These properties have led to the investigation of RGD peptides and RGD peptide analogs as potential therapeutic agents [ 4 ].

1. Partial primary structure of bovine plasma fibronectin: three types of internal homology. Proc. Natl. Acad. Sci. U.S.A. 80, 137-41
2. Proposed acquisition of an animal protein domain by bacteria. Proc. Natl. Acad. Sci. U.S.A. 89, 8990-4
3. Structure of a fibronectin type III domain from tenascin phased by MAD analysis of the selenomethionyl protein. Science 258, 987-91
4. 2.0 A crystal structure of a four-domain segment of human fibronectin encompassing the RGD loop and synergy region. Cell 84, 155-64