Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1062 Chapter 19: Cell Junctions and the Extracellular Matrix
Figure 19–39 The structure of a typical collagen molecule. (A) A model of
part of a single collagen α chain, in which each amino acid is represented by
a sphere. The chain is about 1000 amino acids long. It is arranged as a lefthanded
helix, with three amino acids per turn and with glycine as every third
amino acid. Therefore, an α chain is composed of a series of triplet Gly-X-Y
sequences, in which X and Y can be any amino acid (although X is commonly
proline and Y is commonly hydroxyproline, a form of proline that is chemically
modified during collagen synthesis in the cell). (B) A model of part of a
collagen molecule, in which three α chains, each shown in a different color,
are wrapped around one another to form a triple-stranded helical rod. Glycine
is the only amino acid small enough to occupy the crowded interior of the
triple helix. Only a short length of the molecule is shown; the entire molecule
is 300 nm long. (From a model by B.L. Trus.)
Collagens are extremely rich in proline and glycine, both of which are important
in the formation of the triple-stranded helix.
The human genome contains 42 distinct genes coding for different collagen α
chains. Different combinations of these genes are expressed in different tissues.
Although in principle thousands of types of triple-stranded collagen molecules
could be assembled from various combinations of the 42 α chains, only a limited
number of triple-helical combinations are possible, and roughly 40 types of collagen
molecules have been found. Type I is by far the most common, being the
principal collagen of skin and bone. It belongs to the class of fibrillar collagens,
or fibril-forming collagens: after being secreted into the extracellular space, they
assemble into higher-order polymers called collagen fibrils, which are thin structures
(10–300 nm in diameter) many hundreds of micrometers long in mature
tissues, where they are clearly visible in electron micrographs (Figure 19–40; see
also Figure 19–38). Collagen fibrils often aggregate into larger, cablelike bundles,
several micrometers in diameter, that are visible in the light microscope as collagen
fibers.
Collagen types IX and XII are called fibril-associated collagens because they
decorate the surface of collagen fibrils. They are thought to link these fibrils to
one another and to other components in the extracellular matrix. Type IV is a
network-forming collagen, forming a major part of basal laminae, while type VII
molecules form dimers that assemble into specialized structures called anchoring
fibrils. Anchoring fibrils help attach the basal lamina of multilayered epithelia
to the underlying connective tissue and therefore are especially abundant in the
skin. There are also a number of “collagen-like” proteins containing short collagen-like
segments. These include collagen type XVII, which has a transmembrane
domain and is found in hemidesmosomes, and type XVIII, the core protein of a
proteoglycan in basal laminae.
Many proteins appear to have evolved by repeated duplications of an original
DNA sequence, giving rise to a repetitive pattern of amino acids. The genes that
encode the α chains of most of the fibrillar collagens provide a good example: they
are very large (up to 44 kilobases in length) and contain about 50 exons. Most of
(A)
(B)
y
x
y
x
glycine
y
x
y
x
y
x
y
x
y
x
y
x
y
x
y
x
1.5 nm
MBoC6 m19.62/19.40
1 µm
Figure 19–40 A fibroblast surrounded by
collagen fibrils in the connective tissue
of embryonic chick skin. In this electron
micrograph, the fibrils are organized into
bundles that run approximately at right
angles to one another. Therefore, some
bundles are oriented longitudinally, whereas
others are seen in cross section. The
collagen fibrils are produced by fibroblasts.
(From C. Ploetz, E.I. Zycband and
D.E. Birk, J. Struct. Biol. 106:73–81, 1991.
With permission from Elsevier.)