chapter 11
Heteropolysaccharides II: Proteoglycans and Peptidoglycans
A major fibrillar component is a glycoprotein called
The structure of fibrillin consists of several
cysteine-rich motifs and exhibits a multidomain organi-
zation similar to epidermal growth factor. The structure
is stabilized by disulfide linkages. Fibrillin monomers
undergo aggregation extracellularly into supramolecular
structures. The fibrillar structures have a diameter of
1 0 - 1 2
nm and surround the amorphous component elastin.
During fetal development, the fibrillar component appears
first in the extracellular matrix. With increasing fetal age
and with maturation of the fibers the amorphous compo-
nent is deposited within the framework of the microfibrillar
bundles producing mature, elastic microfibrils.
Fibrillin is encoded by a gene located in the long arm of
chromosome 15. Mutations in the fibrillin gene lead to an
autosomal dominant trait known as
Marfan’s syndrome.
The incidence of this disorder is 1:10,000, and 15-30%
of cases are caused by new mutations in the fibrillin gene.
Consistent with the function of fibrillin in the elastic
connective tissues, the clinical manifestations present
disorders of cardiovascular,
opthalmic systems. For example, dissecting aneurysm of
the aorta, preceded by a dilatation, is a potentially fatal
cardiac manifestation.
Mature elastin is a linear polypeptide,
which has a molecular weight of about 72,000 and contains
about 850 amino acid residues. Although glycine accounts
for one third of the residues, the repeat sequence Gly-
X-Y characteristic of collagen is not present in elastin.
Instead, glycine residues are present in the repeat units
Gly-Gly-Val-Pro, Pro-Gly-Val-Gly-Val, and Pro-Gly-
Val-Gly-Val-Ala. Elastin is relatively rich in the nonpo-
lar amino acids; alanine, valine, and proline. In contrast to
collagen, only a few hydroxyproline residues are present
in elastin. Elastin contains no hydroxylysine or sugar
A feature of mature elastin is the presence of covalent
cross-links that connect elastin polypeptide chains into a
fiber network. The major cross-linkages involve desmo-
sine and isodesmosine, both of which are derived from
lysine residues. Several regions rich in lysine residues can
provide cross-links. Two such regions that contain peptide
sequences that are repeated several times in tropoelastin
have the primary structure -Lys-Ala-Ala-Ala-Lys- and
Formation of desmosine and isodesmosine covalent cross-links in elastin. Three allysine residues (R
, R
, and
) and one lysyl residue (Ri) condense to give a desmosine cross-link. The allysine residues (s-aldehydes) are
derived from the oxidative deamination of lysyl residues. The isodesmosine cross-link is formed similarly,
except that it contains a substitution at position 2 rather than at position 4, along with substitutions at 1, 3, and 5
on the pyridinium ring.
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