Lysine post-translational modifications of collagen

Abstract

Type I collagen is the most abundant structural protein in vertebrates. It is a heterotrimeric molecule composed of two α1 chains and one α2 chain, forming a long uninterrupted triple helical structure with short non-triple helical telopeptides at both the N- and C-termini. During biosynthesis, collagen acquires a number of post-translational modifications, including lysine modifications, that are critical to the structure and biological functions of this protein. Lysine modifications of collagen are highly complicated sequential processes catalysed by several groups of enzymes leading to the final step of biosynthesis, covalent intermolecular cross-linking. In the cell, specific lysine residues are hydroxylated to form hydroxylysine. Then specific hydroxylysine residues located in the helical domain of the molecule are glycosylated by the addition of galactose or glucose-galactose. Outside the cell, lysine and hydroxylysine residues in the N- and C-telopeptides can be oxidatively deaminated to produce reactive aldehydes that undergo a series of non-enzymatic condensation reactions to form covalent intra- and inter-molecular cross-links. Owing to the recent advances in molecular and cellular biology, and analytical technologies, the biological significance and molecular mechanisms of these modifications have been gradually elucidated. This chapter provides an overview on these enzymatic lysine modifications and subsequent cross-linking.

Thermal stability of collagen in naturally ageing and in vitro glycated rabbit tissues

“…The temperature of denaturation in corneal samples was not different between young mature (Y-C) and ageing (A-C) groups (Table 1). Accounting for the fact that after maturation of the tissue the only possible change in crosslinking profile of collagen can be caused by glycation [2,3], a similarly low level of advanced glycation end products (AGEs) in both age groups could be inferred. That conclusion is confirmed by fluorescence intensity which was very low in samples from both young mature and ageing rabbits (Fig.…”

“…Formation of all collagen fibres is based on similar biochemical pathways-posttranslational modifications of lysine residues [2,3]. However, both the extent of hydroxylation of lysine in the molecules and the presence of other matrix constituents result in the diversity of structures among collagen based tissues.…”

“…Moreover, the structure of collagenous matrix in the same tissue changes during maturation and ageing as a result of enzymatic and non-enzymatic crosslinking residues. Lysyl oxidase-mediated reactions involving lysine and hydroxylysine residues result in crosslinks which spontaneously stabilize forming a mature collagen network responsible for the functional integrity of the tissue [3,4]. Non-enzymatic reactions between collagen and sugars result in various advanced glycation end products (AGEs) that form additional intermolecular crosslinks or protein adducts [5].…”

Mechanisms of Lung Fibrosis Resolution

“…One family of enzymes mediating this cross-linking is lysyl oxidase and its homologues (lysyl oxidaseelike enzymes 1 to 4). 31 The lysyl oxidases catalyze the oxidation of primary amines, such as lysine residues into aldehydes. These aldehydes then react with other aldehydes or amines to cross-link collagen or elastin.…”

Identification of Glycopeptides with Multiple Hydroxylysine O-Glycosylation Sites by Tandem Mass Spectrometry

“…[40][41][42] The error tolerance for precursor masses was set as 0.02 Da. Since the CID and ETD spectra were collected in the linear ion trap of the mass spectrometer, the error tolerance for CID and ETD fragment masses was set as 0.5 Da.…”