Triple helix collagen conformation

The ability of these peptidomimetic collagen-structures to adopt triple helices portends the development of highly stable biocompatible materials with collagenlike properties. For instance, it has been found that surface-immobilized (Gly-Pro-Meu)io-Gly-Pro-NH2 in its triple-helix conformation stimulated attachment and growth of epithelial cells and fibroblasts in vitro [77]. As a result, one can easily foresee future implementations of biostable collagen mimics such as these, in tissue engineering and for the fabrication of biomedical devices. 

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. ... 

Another type of helix occurs in the collagens, which are important constituents of the con-nectivetissue matrix (see pp. 70, 344). The collagen helix is left-handed, and with a pitch of 0.96 nm and 3.3 residues per turn, it is steeper than the a-helix. In contrast to the a-helix, H bonds are not possible within the collagen helix. However, the conformation is stabilized by the association of three helices to form a righthanded collagen triple helix (see p. 70). 

Figure 2.15. Conformational plot showing location of a helix, (3 sheet, and collagen triple helix. The plot shows the locahzation of the predominant chain structures found in proteins, including the a helix (a), (3 sheet ((3), and collagen triple helix (C).The it stands for a helix that does not occur in nature.

Recently it has been demonstrated, by analysis of the flexibility from conformation maps of dipeptide sequences, that the collagen triple helix contains rigid domains separated by domains with increased flexibility (see Figure 2.23) (see Silver et 2003, for a review). Autocorrelation of the peptide sequences in collagen, using Fourier analysis, demonstrates that there is a period of the flexible domains in both the molecule and... 

The four protein conformations that provide mechanical stability to cells, tissues, and organs include the random coil or amorphous structure that characterizes a part of the structure of elastin, the a helix, which is represented by the keratin molecule, the collagen triple helix, and the p structure of silk. In humans the P structure is found only in short sequences connecting parts of other structures such as the a helix, but serves as an example of the relationship between protein structure and properties. The ultimate tensile strength and modulus of each structure differs as discussed below. 

Figure 2.46 Conformation of a single strand of a collagen triple helix.

Next, we discuss the collagen, which takes the triple helix structure. The amino acid sequence of collagen fibril consists of the repeating amino-acid sequence unit [Gly-Xaa-Yaa]n, where Xaa and Yaa are frequently occupied by prolyl (Pro) and 4-hydroxyprolyl (Hyp) residues, respectively. It is well known that the sequential model polypeptides such as [Pro-Ala-Gly]n or [Pro-Pro-Gly]n take the triple-helix conformation similar to that of collagen, as studied by X-ray diffraction and C, N CP-MAS NMR. This section focuses on the structure of [Pro-Ala-Gly]n, and the collagen structure as described by H CRAMPS NMR. 

In the context of the collagen triple helix it can be concluded that the Cf-exo pucker of the proline in Yaa position is favored by stereoelectronic effects of a (4R)-OH substituent which also stabilizes the traus-Xaa-(4R)-Hyp peptide bond, thus preorganizing this residue in a conformation that best befits a triple helix. Conversely, in the Xaa position the Pro residue is preferred in the Cy-endo pucker the related dihedral angles are reported in Table 11.3. 

The substrate specificity of prolyl hydroxylase has been well studied. Native collagen is not hydroxylated to its fullest extent and can serve as a substrate for the enzyme. Collagen cannot undergo hydroxylation in the triple-helix conformation but must first be denatured to the random-... 

Figure 1.31 Cartoon depiction of the right-handed collagen triple helix. Depiction emphasises how three polypeptides in Left-handed Pn helical conformations associate to form the triple helical structure wherein each polypeptide adopts a gentle right-handed rope-like twist in order to maximise stabilising inter-chain hydrogen bond interactions. Structure is also stabilised by a sheath of ordered water molecules of solvation (illustration from Voet, Voet Pratt, 1999 [Wiley], Fig. 6-17).

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