180

chapter 11

Heteropolysaccharides II: Proteoglycans and Peptidoglycans

A major fibrillar component is a glycoprotein called

fibrillin.

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

as

disorders of cardiovascular,

musculoskeletal,

and

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,

tropoelastin,

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

residues.

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

FIGURE 11-5

Formation of desmosine and isodesmosine covalent cross-links in elastin. Three allysine residues (R

2

, R

3

, and

R

4

) 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.