Collagen Structure: The Madras Triple Helix and the Current Scenario

Abstract

This year marks the 50th anniversary of the coiled-coil triple helical structure of collagen, first proposed by Ramachandran's group from Madras. The structure is unique among the protein secondary structures in that it requires a very specific tripeptide sequence repeat, with glycine being mandatory at every third position and readily accommodates the imino acids proline/hydroxyproline, at the other two positions. The original structure was postulated to be stabilized by two interchain hydrogen bonds, per tripeptide. Subsequent modeling studies suggested that the triple helix is stabilized by one direct inter chain hydrogen bond as well as water mediated hydrogen bonds. The hydroxyproline residues were also implicated to play an important role in stabilizing the collagen fibres. Several high resolution crystal structures of oligopeptides related to collagen have been determined in the last ten years. Stability of synthetic mimics of collagen has also been extensively studied. These have confirmed the essential correctness of the coiled-coil triple helical structure of collagen, as well as the role of water and hydroxyproline residues, but also indicated additional sequence-dependent features. This review discusses some of these recent results and their implications for collagen fiber formation.

Mathematical modeling of collagen turnover in biological tissue

“…The extracellular collagen molecule, procollagen, is made up of three left-handed helix polypeptides, the so-called α-chains, coiled-up in a right-handed helical structure, about 300 nm long and 1.5 nm in diameter (Bella et al, 1994;Orgel et al, 2001;Bhattacharjee & Bansal, 2005). Collagen molecules assemble along a given direction through covalent bonds to form collagen microfibrils, constituting the basic building block of collagen fibrils (Baselt et al, 1993;Hulmes et al, 1995;Orgel et al, 2006Orgel et al, , 2011.…”

Glyphosate pathways to modern diseases VI: Prions, amyloidoses and autoimmune neurological diseases

“…Those that are released can be expected to produce defective collagen matrices. Collagen is even more highly enriched in glycine than in proline, as its core structure consists of a triple peptide repeat, where glycine is always the third residue of the triplet, and proline and hydroxproline often occupy the other two positions [128]. Glyphosate substitution for glycine in structural proteins; i.e., collagen, elastin, fibronectin and laminin; would contribute to disrupted folding as well as defective strength and elasticity.…”

Determination of Hydroxyproline in Collagen Biomaterials for Medical Use and Validation of Method

“…Ponderile reziduului hidroxiprolil din colagenul tip II din cartilaje ºi colagenul tip IV din membranele bazale sunt cuprinse între 12,9% ºi 14,3% ºi sunt de aproximativ 15,0% în colagenul de tip III [9,10].…”

“…The ratio of hydroxyprolyl residue in type II collagen from cartilage and in type IV collagen from basement membranes ranges from 12.9% and 14.3%, and is approximately 15.0% in type III collagen [9,10].…”