A major component of the extracellular matrix. Fibronectin is a large, filamentous protein involved in an incredible number of cellular processes including embryogenesis, wound healing, cell adhesion and the pathogenesis of many diseases. In addition to physiological roles, fibronectins have interesting structural properties that have implications for understanding other aspects of biological machinery (biomachinery?).

Physical Structure:
One of the interesting things about fibronectin is that, although it is a huge, huge protein (over 2500 amino acids), its structure is actually composed of tandem repeats of particular domains. These repeats fall into three categories:

Fibronectin starts off with 5 type I domains, then a mixture of type I and II domains, followed by a large string of 17 or more type III domains. The tail then has three more type I domains. It is believed that these multiple repeats are the result of gene duplication events during evolution which have made the protein longer and allowed it to accomodate multiple functional binding sites. crystal structures have been solved for type II and III domains showing them to have a beta-sandwich type fold. These domains are also found in numerous other proteins, such as cell surface receptor, which are involved in signalling pathway. Again, these domains are believed to have found their way into other proteins through gene duplication and insertion events. Type III domains, in particular, are useful because of their high degree of sequence plasticity, allowing them to bind a large number of different targets. Another class of proteins capable of this is the immunoglobulin superfamily (IgSF), which are also beta-sandwich folds.

Physiological Roles: One major role of fibronectin is making cell to extracellular matrix (ECM) connections. Because of fibronectin's multi-domain nature ... it is very elastic. Each domain unfolds like a little spring, giving you a long spring. This allows tissues to have some flex and give to them. Cells adhere through these flexible linkers to the tough collagen rich ECM, giving tissue both strength and flexibility. Fibronectin serves a related role in wound healing. It is a critical component of the provisional matrix, a gel of protein and cells which provides the foundation for other molecules involved in the healing process to anchor and serve their roles. It may also play a role in adhesion of platelets to the wound site. It is directly involved in building the scaffold that helps repair damage to the kidney during renal diseases. It is believed to play a similar role in lung repair as well.

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