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

1066 Chapter 19: Cell Junctions and the Extracellular Matrix
elastic fiber
Figure 19–45 Stretching a network of
elastin molecules. The molecules are
joined together by covalent bonds (red)
to generate a cross-linked network. In
this model, each elastin molecule in the
network can extend and contract in a
manner resembling a random coil, so that
the entire assembly can stretch and recoil
like a rubber band.
STRETCH
RELAX
single elastin molecule
cross-link
elastin and is essential for the integrity of elastic fibers. Mutations in the fibrillin
gene result in Marfan’s syndrome, a relatively common human disorder. In the
most severely affected individuals, the aorta is prone to rupture; other common
effects include displacement of the lens and abnormalities of the skeleton and
joints. Affected individuals are MBoC6 often m19.71/19.46
unusually tall and lanky: Abraham Lincoln is
suspected to have had the condition.
Fibronectin and Other Multidomain Glycoproteins Help Organize
the Matrix
In addition to proteoglycans, collagens, and elastic fibers, the extracellular matrix
contains a large and varied assortment of glycoproteins that typically have multiple
domains, each with specific binding sites for other matrix macromolecules
and for receptors on the surface of cells (Figure 19–46). These proteins therefore
contribute to both organizing the matrix and helping cells attach to it. Like the
proteoglycans, they also guide cell movements in developing tissues, by serving
fibronectin
N
CYR61
N
tenascin
N
N
fibrin collagen integrin heparin
C
thrombospondin
KEY TO REPEAT DOMAINS
FN1 FN2 FN3 EGF
C
TSPN TSP1 TSP3 TSP_C IGFBP
VWC C-term cys knot FBG + alternatively spliced exons
C
fibrin
C
Figure 19–46 Complex glycoproteins
of the extracellular matrix. Many matrix
glycoproteins are large scaffold proteins
containing multiple copies of specific
protein-interaction domains. Each domain
is folded into a discrete globular structure,
and many such domains are arrayed
along the protein like beads on a string.
This diagram shows four representative
proteins among the roughly 200 matrix
glycoproteins that are found in mammals.
Each protein contains multiple repeat
domains, with the names listed in the key
at the bottom. Fibronectin, for example,
contains numerous copies of three different
fibronectin repeats (types I–III, labeled
here as FN1, FN2, and FN3). Two type
III repeats near the C-terminus contain
important binding sites for cell-surface
integrins, whereas other FN repeats are
involved in binding fibrin, collagen, and
heparin, as indicated (see Figure 19–47).
Other matrix proteins contain repeated
sequences resembling those of epidermal
growth factor (EGF), a major regulator
of cell growth and proliferation; these
repeats might serve a similar signaling
function in matrix proteins. Other proteins
contain domains, such as the insulin-like
growth factor-binding protein (IGFBP)
repeat, that bind and regulate the function
of soluble growth factors. To add more
structural diversity, many of these proteins
are encoded by RNA transcripts that
can be spliced in different ways, adding
or removing exons, such as those in
fibronectin. Finally, the scaffolding and
regulatory functions of many matrix
proteins are further expanded by assembly
into multimeric forms, as shown at the
right: fibronectin forms dimers linked
at the C-termini, whereas tenascin and
thrombospondin form N-terminally linked
hexamers and trimers, respectively.
Other domains include four repeats from
thrombospondin (TSPN, TSP1, TSP3,
TSP_C). VWC, von Willebrand type C;
FBG, fibrinogen-like. (Adapted from
R.O. Hynes and A. Naba, Cold Spring
Harb. Perspect. Biol. 4:a004903, 2012.)