Fibronectin

Molecular structure of fibronectin

The fibronectin molecule is a large glycoprotein. The basic structure of this compound is formed strictly by two polypeptide chains. To ensure spatial stability, these chains are inextricably linked to each other via strong disulfide bonds (S–S bonds). According to structural models, these covalent bonds are localized near the C-terminal regions of the molecule.

The most important feature of the molecular structure is a clearly defined domain organization. Each of the two polypeptide chains is divided into 7–8 functional domains. It is the presence of these isolated regions (centers) that determines the unique ability of the molecule to simultaneously interact with a huge number of various cellular structures and extracellular matrix components, acting as a universal connecting element.

Specific binding sites

The uniqueness of fibronectin lies in the presence of numerous specific binding sites. These highly specific regions, located on the domains of the polypeptide chains, allow the molecule to act as a multifunctional linking link. The glycoprotein is capable of selectively and tightly binding the following components of the extracellular environment:

• Cell surface: interaction is carried out with the participation of specific cell receptors — integrins.
• Collagen fibers: the molecule has a separate, strictly determined binding site for collagen.
• Proteoglycans and heparan sulfates: sites for their binding are distributed on both polypeptide chains of fibronectin.
• Hyaluronic acid: interaction occurs via a specialized binding site.
• Carbohydrate components: fibronectin actively binds to carbohydrates that are part of the plasma membranes of cells.
• Enzymes: binding to a specific enzyme — transglutaminase — has been proven.

Biological functions in tissues

Synthesized and secreted into the intercellular space by a vast number of diverse cell types, fibronectin undertakes two fundamental biological tasks:

1. Integrating function. The molecule takes an active part in the global organization of the intercellular substance. Thanks to multiple domains, it binds disparate matrix components together, creating a unified spatial network.
2. Adhesive function. The glycoprotein acts as an effective molecular fixative. It repeatedly enhances and promotes cell adhesion — the reliable attachment of cells to surrounding structures of the intercellular space.

Role of fibronectin in oncology (metastasis)

The study of fibronectin is of critical importance for clinical medicine, primarily for understanding pathological processes in oncology. During malignant transformation of cells, major changes in the molecular composition of their surface are observed. In particular, a sharp decrease in the amount of this glycoprotein is registered on the plasma membrane of tumor cells.

A direct consequence of fibronectin deficiency is the loss of strong intercellular contacts. Malignant cells become significantly less firmly bound both to each other and to the surrounding extracellular matrix. Such weakening of adhesive properties critically facilitates their detachment from the primary tumor locus and subsequent migration through the body. The described molecular defect underlies the process of metastasis — a key and most dangerous stage of cancer progression.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Structure and functions of integrin receptors
• Interaction of glycoproteins with the enzyme transglutaminase
• Role of hyaluronic acid and proteoglycans in matrix structure
• Molecular mechanisms of cell adhesion

Other topics in the section "Biochemistry of the Extracellular Matrix"

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