Conformation and Chemical Structure
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 haphazardly folded ball.
The amino acid profile of the protein is extremely specific. The overwhelming majority (70%) consists of hydrophobic amino acids with small side chains. A small amount of hydroxyproline is also present. Protein molecules assemble into an extensive network, forming fibers and sheets through numerous strong cross-links.
Stretch Mechanism and the Hydrophobic Effect
The rubber-like properties of the tissue are driven by two factors: the presence of a random conformation and a high density of covalent cross-links. The entire process of stretching and recoil is governed by thermodynamics and hydrophobic interactions.
- Resting state. Polypeptide chains are folded into disordered globules. The system is at maximum entropy: hydrophobic side chains minimize contact with the surrounding aqueous environment by "hiding" within the structure.
- Stretching. Under mechanical stress, molecules straighten and align along the axis of tension. Hydrophobic regions are forcibly exposed to water. System order increases, and entropy drops sharply. However, the molecules do not pull apart from one another due to covalent cross-links.
- Recoil. As soon as the load is removed, the hydrophobic effect instantly drives the molecules back to their original folded state.
Cross-Links: Desmosine and Lysinonorleucine
Elastin molecules are bound into a unified framework by unique structures. The main types of cross-links are lysinonorleucine (joining two lysine residues) and desmosine.
Desmosine is a specialized amino acid formed from four lysine residues that can cross-link up to four polypeptide chains simultaneously. The bonds within desmosine (forming a pyridine-like ring structure) are so strong that they resist even acid hydrolysis.
The cross-linking process occurs via post-translational modification:
- The extracellular enzyme lysyl oxidase catalyzes the oxidative deamination of $\varepsilon$-amino groups of lysine.
- This yields reactive aldehydes—allysine radicals.
- Condensation of allysine and lysine yields lysinonorleucine, whereas three allysine molecules and one lysine molecule form desmosine.
Lysyl oxidase activity requires copper ions ($Cu^{2+}$), vitamin $B_6$ (pyridoxal phosphate), and niacin (vitamin $B_3$/$PP$).
Pathologies of Elastin Metabolism
If cross-linking is disrupted, the elastic framework of organs loses its structural integrity.
Main causes of pathology:
- Impaired desmosine formation.
- Defects in synthesis enzymes (lysyl oxidase).
- Impaired absorption of copper, which acts as a cofactor for enzymatic reactions.
Clinical manifestations: Defects in elastin metabolism affect organs subject to regular mechanical stress. This leads to severe heart valve defects, aortic aneurysms, pulmonary emphysema, and severe varicose veins.