Elastin

Conformational and chemical structure features

Unlike most other proteins, elastin peptide chains lack a characteristic ordered tertiary structure. In the extracellular matrix, they maintain a flexible random coil conformation, resembling a randomly tangled ball.

The amino acid profile of the protein is extremely specific. The overwhelming majority (70%) is represented by hydrophobic amino acids with small side chains. A minor amount of hydroxyproline is also present. Protein molecules assemble into an extensive network, forming fibers and sheets with the help of numerous strong cross-links.

Stretching mechanism and hydrophobic effect

The rubber-like properties of the tissue are due to two factors: the presence of a random conformation and a large number of covalent cross-links. The entire process of stretching and compression is governed by the laws of thermodynamics and hydrophobic interactions.

1. Resting state. Polypeptide chains are coiled into disordered globules. The system is in a state of entropy maximum: hydrophobic side chains minimize contact with the surrounding aqueous environment by "hiding" inside the structure.
2. Stretching. Under mechanical stress, molecules straighten and orient along the tension axis. Hydrophobic regions are forced to come into contact with water. The order of the system increases, and entropy drops sharply. At the same time, molecules do not pull apart from each other thanks to cross-links.
3. Shape recovery. As soon as the load is removed, the hydrophobic effect instantly returns the molecules to their original coiled state.

Cross-links: desmosine and lysinonorleucine

Elastin molecules are linked into a unified framework by unique structures. The main types of cross-links are lysinonorleucine (connecting two lysine residues) and desmosine.

Desmosine is a specific amino acid formed from four lysine residues and capable of binding up to four polypeptide chains simultaneously. The bond within desmosine (a structure resembling a pyridine ring) is so strong that it resists even acid hydrolysis.

The process of cross-link formation occurs via post-translational modification:

• The extracellular enzyme lysyl oxidase catalyzes the oxidative deamination of lysine $\varepsilon$-amino groups.
• This results in the formation of reactive aldehydes — allysine radicals.
• Condensation of allysine and lysine yields lysinonorleucine, while three molecules of allysine and one molecule of lysine form desmosine.

Lysyl oxidase activity requires copper ions ($Cu^{2+}$), vitamin $B_6$ (pyridoxal phosphate), and vitamin $PP$.

Elastin metabolism disorders

If the cross-linking process is disrupted, the elastic framework of organs loses its strength.

Main causes of pathologies:

• Impaired desmosine formation.
• Defects in enzymes involved in synthesis (lysyl oxidase).
• Problems with the absorption of copper, which acts as a cofactor for enzymatic reactions.

Clinical manifestations: Disruptions in elastin metabolism hit organs that regularly undergo stretching. This leads to severe heart valve defects, development of aortic aneurysms, pulmonary emphysema, and severe varicose veins.

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Mechanism of oxidative deamination of lysine by lysyl oxidase
• Comparative characteristics of the amino acid composition of collagen and elastin
• The role of vitamins B6 and PP in the biosynthesis of extracellular matrix components
• Pathogenesis of pulmonary emphysema during the destruction of elastic fibers

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

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