Around the collagen triple helix: an introduction to studying associated genetic and acquired diseases

The triple helix structure of collagen is the most abundant motif found in our bodies. It is believed to have emerged during the transition from unicellular to multicellular animal organisms, known as metazoans, and has evolved into various proteins that contribute to the development and function of diverse animal tissues, organs, and systems. Once synthesized, these collagenous proteins undergo post-translational modifications and proper folding inside the cell, after which they primarily function outside the cell. Over 80 collagenous proteins are categorized into two main groups: collagens and collagen-like proteins. However, the distinction between these groups is not clearly defined. Within these categories, there are various types of proteins, including soluble proteins, transmembrane proteins, and those that form the extracellular matrix. Multiple genetic diseases highlight the significance of collagenous proteins, which can be affected by defects in their primary structure, post-translational modifications, or complete loss. While fixing the gene defect may seem like a straightforward solution, we currently lack the capability to do so. Moreover, acquired diseases caused or accompanied by adverse processes in the collagen triple helix are generally not suitable for gene therapy at all. Understanding the pathogenicity of a defective polypeptide chain can provide valuable insights into strategies for mitigating negative consequences for both genetic and acquired diseases. This review highlights the current state of research in the collagen triple helix field, offering insights into how to study specific defects and deepen our understanding of their underlying pathogenic mechanisms.