Covalent cross-links, collagen

Collagen triple helices are stabilized by hydrogen bonds between residues in dijferent polypeptide chains. The hydroxyl groups of hydroxyprolyl residues also participate in interchain hydrogen bonding. Additional stability is provided by covalent cross-links formed between modified lysyl residues both within and between polypeptide chains. 

Some proteins, like collagen and elastin, have covalent cross-links between their fibres, which are formed after their synthesis (post-translational modification). 

Covalent cross-linking of collagen chains adds markedly to the strength of the triple helix as well as to the larger structures formed by these connections. 

Lateral association of collagen molecules followed by covalent cross-linking... 

The primary level of structure in a protein is the linear sequence of amino acids as joined together by peptide bonds. This sequence is determined by the sequence of nucleotide bases in the gene encoding the protein (see Topic HI). Also included under primary structure is the location of any other covalent bonds. These are primarily disulfide bonds between cysteine residues that are adjacent in space but not in the linear amino acid sequence. These covalent cross-links between separate polypeptide chains or between different parts of the same chain are formed by the oxidation of the SH groups on cysteine residues that are juxtaposed in space (Fig. 4). The resulting disulfide is called a cystine residue. Disulfide bonds are often present in extracellular proteins, but are rarely found in intracellular proteins. Some proteins, such as collagen, have covalent cross-links formed between the side-chains of Lys residues (see Topic B5). 

Covalent cross-links both between and within the tropocollagen molecules confer strength and rigidity on the collagen fiber. These cross-links are formed between Lys and its aldehyde derivative allysine. Allysine is derived from Lys by the action of the copper-containing lysyl oxidase which requires pyridoxal phosphate for activity. The disease lathyrism is caused by the inhibition of lysyl oxidase by the chemical (3-aminopropionitrile in sweet pea seeds, and results in defective collagen due to the lack of cross-links. 

Figure 2.29. Network structure of laminin in basement membranes. Basement membranes contain a laminin network that is covalently cross-linked to a type IV collagen network.

The free carbonyl residue can further condense with a histidyl group of another polypeptide chain to give a more complex cross-link. Schiff base formation, illustrated in Figure 8.4, involves an allysine residue at either the C- or N-terminal telopeptide and an uncharged lysine or hydroxylysine residue of another properly juxtaposed tropocollagen molecule. Such bonds are therefore intermolecular. Several other types of covalent cross-links are possible in collagens. They almost always involve lysine, allysine, hydroxylysine, hydroxyal-lysine, or histidine. 

Formation of covalent cross-links between molecules Assembly of the collagen fiber... 

Covalent cross-links contribute to the strength of collagen. The first reaction in QUESTION 5.9... 

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