FNIII

FNIII stands for fibronectin type III domain, a modular protein domain common in extracellular matrix and cell-surface proteins. Each FNIII domain is about 90 amino acids long and adopts a beta-sandwich fold. The domain typically lacks disulfide bonds and is stabilized by hydrophobic packing of its beta-sheets.

FNIII domains occur in long tandem arrays in fibronectin, which contains multiple repeats, and are also present in other extracellular matrix proteins such as tenascin, as well as in various cell-surface receptors. The repeats provide platforms for protein interactions and contribute to the mechanical properties and flexibility of the proteins in which they reside.

Functionally, FNIII domains mediate protein–protein interactions and contribute to cell adhesion and signaling. In fibronectin, the FNIII9-10 pair contains an integrin-binding site around the RGD motif in FNIII10, with a nearby synergistic site in FNIII9 that modulates affinity. This arrangement enables specific, regulated engagement with integrin receptors and influences downstream cellular responses.

Biotechnological applications include using FNIII domains as stable, human-derived scaffolds for binding proteins (monobodies). Their small size, robustness, and tolerance of mutations make them attractive for phage display, affinity maturation, and therapeutic or diagnostic development.

Clinically, dysregulation or altered expression of FNIII-containing proteins is linked to diseases involving extracellular matrix remodeling and cancer progression, underscoring the importance of these domains in mediating cell–matrix interactions and signaling.