Abstract
Collagen is a large family of structurally related proteins (1) and is the most abundant molecule in vertebrates. Type I collagen, the predominant genetic type in the collagen family, is a heterotrimeric molecule composed of two α1 chains and one α2 chain and is the major fibrillar component in most connective tissues. This molecule consists of three domains: amino-terminal nontriple helical (N-telopeptide), triple helical (helical), and carboxy-terminal nontriple helical (C-telopeptide) domains (Fig. 1). The central uninterrupted helical domain of each chain contains more than 300 repeats of (Gly-X-Y) sequence and represents more than 95% of the polypeptide. One of the characteristic features of collagen is its extensive posttranslational modifications, most of which are unique to collagen protein. Such modifications include hydroxylation of proline (Pro) and lysine (Lys) residues, glycosylation of specific hydroxylysine (Hyl) residues, oxidative deamination of the e-amino groups of Lys/Hyl in the telopeptide domains of the molecule, and subsequent intra/intermolecular crosslinking (2) (Fig. 1). The hydroxylation of Pro is catalyzed by prolyl 4-hydroxylase and prolyl 3-hydroxylase. The former reacts on Pro with the minimum sequence X-Pro-Gly and the latter appears to require a Pro-4-Hyp-Gly sequence (3). The presence of 4-Hyp (predominant form) is critical in stabilizing the triple helical conformation of collagen providing hydrogen bonds and water bridges (4). The content of Pro/Hyp in type I collagen is relatively high, representing 22–23 of the total amino acids, and 40–45% of Pro is hydroxylated (mostly 4-Hyp).
Structure of type I collagen molecule. Type I collagen molecule is composed of two α1 chains (solid line) and one α2 chain (dotted line). The molecule consists of three domains: amino-terminal nonhelical (N-telo.), central triplehelical (helical), and carboxy-terminal nonhelical (C-telo.) domains. Some of the lysine residues in these domains are hydroxylated. specific hydroxylysine residues in the helical domain can be O-glycosylated to form galactosylhydroxylysine or glucosylgalactosylhydroxylysine residues. In general, the dissaccharide form is more prevalent (20) although the monosaccharide derivative is relatively abundant in certain tissues (e.g., bone). 
Hydroxylysine, -gal: galactose, -glc: glucose, ●: Lysine/Hydroxylysine residues potentially converted to aldehyde.
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Yamauchi, M., Shiiba, M. (2002). Lysine Hydroxylation and Crosslinking of Collagen. In: Kannicht, C. (eds) Posttranslational Modifications of Proteins. Methods in Molecular Biology™, vol 194. Humana Press. https://doi.org/10.1385/1-59259-181-7:277
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DOI: https://doi.org/10.1385/1-59259-181-7:277
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