The Collagen Triple Helix

Collagen, a component of bone and connective tissue, is the most abundant protein in vertebrates. It is organized in water-insoluble fibers of great strength. 

A collagen fiber consists of three polypeptide chains wrapped around each other in a ropelike twist, or triple helix. Each of the three chains has, within limits, a repeating sequence of three amino acid residues, X—Pro—Gly or X—Hyp—Gly, where Hyp stands for hydroxyproline, and any amino acid can occupy the first position, designated by X. 

The three individual collagen chains are themselves helices that differ from the a-helix. They are twisted around each other in a superhelical arrangement to form a stiff rod. This triple helical molecule is called tropocollagen it is 300 nm (3000 A) long and 1.5 nm (15 A) in diameter. The three strands are held together 

Collagen in which the prohne is not hydroxylated to hydroxyproline to the usual extent is less stable than normal collagen. Symptoms of scurvy, such as bleeding gums and skin discoloration, are the results of fragile collagen. The 

---

This gives an important hint at what kind of model peptides are synthesized to obtain detailed information about the thermodynamics and kinetics of the collagen triple-helix formation. A first success was already achieved by synthesizing peptides of the following general structure37 ... 

Engel J, Bachinger H-P (2005) Structure, Stability and Folding of the Collagen Triple Helix. 247 7-33... 

Brodsky, B. and Ramshaw, J.A.M. (1997) The collagen triple-helix structure. Matrix Biology, 15, 545-549. 

Atomic Structures of the Collagen Triple Helix and Collagen Trimerization Domains 510... 

Figure 1 The collagen triple helix, (a) Colored by element C (green), O (red), N (blue), S (yellow) (b) colored by chains and (c) colored by Gly (red), Xaa (yellow), and Yaa (white) positions. The modeis were buiit using PyMOL with the type iii coiiagen model peptide (PDB accession number 3DMW). Glycine residues in every third position are located on the inside of the triple helix. Each chain is staggered by one residue to accommodate the Gly in the center of the triple helix.

Prolyl 4-hydroxylation is the most abundant posttranslational modification of collagens. 4-Hydroxylation of proline residues increases the stability of the triple helix and is a key element in the folding of the collagen triple helix. " In vertebrates, almost all the Yaa position prolines of the Gly-Xaa-Yaa repeat are modified to 4(I( )-hydroxylproline by the enzyme P4H (EC 1.14.11.2), a member of Fe(II)- and 2-oxoglutarate-dependent dioxygenases. This enzyme is an 0 2/ b2-type heterotetramer in which the / subunit is PDI (EC 5.3.4.1), which is a ubiquitous disulfide bond catalyst. The P4H a subunit needs the 13 subunit for solubility however, the 13 subunit, PDI, is soluble by itself and is present in excess in the ER. Three isoforms of the a subunit have been identified and shown to combine with PDI to form [a(I)]2/ 2) [< (II)]2/32> or [a(III)]2/32 tetramers, called the type... 

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. ... 

Despite the requirement ofNC domains for correct oligomerization of the collagen triple helix, the NC domain structures are divergent among all collagens. The structure of the NCI domain of type IV collagen " is... 

Each of the three strands of the collagen triple helix is based upon the poly(Pro)II helix. Numerous studies of peptides capable of triple helix formation have been performed, and these have been reviewed 149 The CD of the collagen triple helix1146 is qualitatively like that of the poly(Pro)II, but the position of the maximum depends on the content of secondary vs tertiary peptide bonds. In natural collagen, the positive band is at about 220 nm and the negative band at 197 nm. 

The tight wrapping of the a chains in the collagen triple helix provides tensile strength greater than that... 

II. The Biological Role and Occurrence of the Collagen Triple-Helix Motif in Proteins... 

---