Collagen side chain position

The availability of high-resolution structures of peptides EKG, T3-785, IBP, and G991-G1032, which include residues other than Pro and Hyp in the X and Y positions, offers the opportunity to investigate the conformation and interactions of side chains from residues typically found within the collagen triple helix. In the peptide with an EKG tripeptide sequence, the Lys and Glu residues did not form direct intermolecular or intramolecular ion pairs, even though such pairs are sterically feasible. ... 

Lysine tyrosylquinone (LTQ). Another copper amine oxidase, lysyl oxidase, which oxidizes side chains of lysine in collagen and elastin (Eq. 8-8) contains a cofactor that has been identified as having a lysyl group of a different segment of the protein in place of the - OH in the 2 position of topaquinone.465 Lysyl oxidase plays an essential role in the crosslinking of collagen and elastin. 

The importance of Gly at every third residue is seen when a mutation in the DNA leads to the incorporation of a different amino acid at just one position in the 1000 residue polypeptide chain. For example, if a mutation leads to the incorporation of Cys instead of Gly, the triple helix is disrupted as the -CH2-SH side-chain of Cys is too large to fit in the interior of the triple helix. This leads to a partly unfolded structure that is susceptible to excessive hydroxy-lation and glycosylation and is not efficiently secreted by the fibroblast cells. This, in turn, results in a defective collagen structure that can give rise to brittle bones and skeletal deformities. A whole spectrum of such mutations... 

In the collagen triple helix, every third residue is positioned toward the center of the helix and comes into close contact with another chain. Only glycine, with its single hydrogen atom side chain, is small enough to fit into this crowded space. 

Having assembled the backbone structures of collagens I and II, specific amino acid side chains may be added. In particular, the incorporation of the Gly.Pro.Hypro sequence (which contributed to the downfall of so many previous models) must be considered. Table VII summarizes the possible positions of various types of side chains in terms of the residue numbering system used in Fig. 10. 

Examination of the model reveals that every third residue, which must lie near the center of the triple helix, can be only glycine (Figure 6.13a). Any side chain would be too bulky. Formation of the individual helices of the collagen type is also favored by the presence of or hydroxyproline in the tropocollagen molecule. A repetitive theme in the sequence is of the form Gly - X - Y, where X is often proline and Y is proline or hydroxyproline. However, other residues are sometimes tolerated in these positions. Like silk fibroin, collagen is a good example of how a particular kind of repetitive sequence dictates a particular structure. 

Each turn of the triple helix contains three amino acid residues, such that every third amino acid is in close contact with the other two strands in the center of the structure. Only glycine, which lacks a side chain, can fit in this position, and indeed, every third amino acid residue of collagen is glycine. Thus, collagen is a polymer of (Gly-X-Y) repeats, where Y is frequently proline or hydroxyproline, and X is any other amino acid found in collagen. 

Figure 1.8 Amino add residue side-chain interactions further restrict free rotation in peptide or polypeptide backbone. Rotational possibilities are defined by allowed values of dihedral angle 4> subtended about N—Co, bond and V subtended about Co,—C(0) bond (left). Theoretically allowed angles are shown in Ramachandran plot (right) together with positions of actual angles found in real protein secondary structures a right-handed a-helix ai. left-handed a-helix parallel/S-sheet f anti-parallel 8-sheet C collagen, Pn helix (see later). (Ramachandran plot from Voet, Voet Pratt, 1999 [Wiley], Fig. 6-6).

All of us are held together by fibrous proteins. A quarter of our body protein is collagen, possibly the most abundant protein on earth. There are actually at least twenty collagens, all very similar in structure, but differently distributed in the animal body. Like silk, collagen is rich in glycine, which occupies every third position in the sequence, and the other abundant amino acid is proline. This amino acid is unique in that its side chain makes a loop, attached at its other end to the nitrogen atom of the polypeptide backbone thus ... 

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