Chemistry Reference
In-Depth Information
The designation “type I” collagen indicates that several different collagens exist,
and, in fact, “collagen” is now used to denote members of a large family of proteins that
share certain common features. More than 40 vertebrate genes have been identified as
members of the collagen family (Pace et al. 2003), and there are related genes in
invertebrates as distant as sponges, sea urchins, and the byssus threads of mussels (Lucas
et al. 2002; Boot-Handford and Tuckwell 2003). The key feature defining a collagen is
the presence of continuous or interrupted sequences in the individual polypeptide chains
of repeated (GXY)
n
amino acid sequence domains. (In the single letter abbreviations for
amino acids, G is Glycine while X and Y may be any amino acid.) These domains on one
polypeptide chain interact with similar domains on two additional chains to form
compound triple-helical units with characteristic folding, the “collagen-fold.” In the
collagen fold domains, the X and Y chain positions can accommodate any amino acids
except cysteine and tryptophan. In the vertebrate collagens, X is frequently P (proline)
and Y is P or O (hydroxyproline). The 40 different chains can assemble into
homotrimeric or heterotrimeric triple-helical structures, with the requirement that the
lengths of the (GXY)
n
domains on each chain must match the lengths on the partner
chains so that stable triple-helical segments can be formed. As of this time, 27 different
combinations of chains have been recognized as assembled into distinct molecules.
The molecular forms have been grouped into several broad classes: fibrillar collagens,
types I, II, III, V, XI, XXIV and XXVII, which are all characterized by a long uninterrupted
triple helix containing 300 or more GXY repeats; network forming collagen, type IV, with
shorter interrupted triple-helix segments joined by more flexible, hinged chain regions
(Blumberg et al. 1987, 1988) so that three-dimensional nets can be formed; and the
remaining FACIT or fibril-associated collagens with interrupted triple helix (Olsen et al.
1989) that may be involved in linking other extracellular matrix components to the fibrillar
matrix or in regulating fibril size or other properties. In all cases the triple-helical domains
are bounded by “noncollagenous” (NC) sequence domains that do not fold into triple-
helical conformations, although in the three-chain assembly interactions of both covalent
and non-covalent nature may form between NC domains. The collagens of primary
importance to this discussion of the vertebrate mineralized tissues are the fibrillar
collagens. At the protein level, collagens I, II, and III are the major fibrillar collagens,
while collagen types V, XI, XXIV and XXVII are present in minor amounts. All of the
fibrillar collagens are related in terms of their gene structure as well as amino acid
structure. The exons of the fibrillar collagen genes within the triple helical regions all
appear to have been derived by gene duplication from a primordial 54 base pair (18 amino
acid, [GXY]
6
coding) gene. Type I, V and XI collagens form heterotrimers, with types I
and XI having two chains, designated COL1A1 and COL1A2, and COL11A1 and
COL11A2, respectively. Type V forms heterotrimers built from COL5A1, COL5A2,
COL5A3 chains. Type II molecules are homotrimers comprised of COL2A1 chains, and
similarly type III is comprised of three COL3A1 chains. Types XXIV and XXVII are
probably homotrimers constructed from COL24A1 and COL27A1 chains, respectively.
Phylogenetic analyses show the major and minor fibrillar collagens separate into
three clades, Figure 5. The organization of the exons of different sizes within the triple
helical regions is different in detail in each case but leads to the same type of major triple
helix. However, a major difference can be seen in Figure 6 (Välkkilä et al. 2001; Pace et
al. 2003) relating to the NC domains flanking the major helix. Clearly, the composite N-
terminal NC domains of the three lineages are quite different; the minor fibrillar
collagens all have very large and complex N-terminal NC domains as compared to the
much smaller N-terminal NC domains of the major fibrillar collagens. On the other hand,
although they are different and have been used to distinguish the phylogenetic
relationships of the fibrillar collagens, the C-terminal NC domains are similar in
