Chemistry Reference
In-Depth Information
Table 11.2
Main functions of PG s .
PG type
Main functions
Extracellular PGs (ACAN,
VCAN, BCAN, NCAN)
High viscosity and elasticity causes adsorption of large volumes
of water. Maintenance tensile strength of skin and tendon and
compressive properties of cartilage. Mineralized matrix of bones.
Involved in cellular attachment, cell proliferation and differentia-
tion by interacting with cell surfaces and extracellular matrix
molecules.
SLRPs (DCN, BCN, LUM)
Interact with collagens (types I, III, VI, XII and XIV) that form
the framework of the extracellular matrix. Core protein of SLRPs
interacts with fi brillar collagen, fi bril/fi bril interaction of DS
chains (DCN and BCN) regulates collagen fi bril diameter and
stabilizes the collagen network. DNC/BCN protein core binds
growth factors and infl uences their bioactivity.
Basement membrane PGs
(HSPG2, AGRN, Collagen
XVIII)
Bind to and cross-link themselves and glycan-free matrix com-
ponents to form fl exible thin mats with a wide range of regula-
tory functions including permeability control. Selective barrier
for macromolecules. Control invasion of cancer cells. Adhesive
matrix for endo- and epithelial cells.
Cell - surface PGs (SDC1 - 4,
GPC1 - 6)
Act as coreceptors for growth factors, mediate cell-cell and cell-
matrix adhesion, modulate the activity of enzymes and their
inhibitors, are low-affi nity receptors of enzymes and serve as
attachment sites for blood cells and viruses. The ectodomain can
be enzymatically released ('shedding') and thereby modulates
various biological processes. The cytosolic domain is involved in
intracellular signaling, adhesion of cell skeleton structures and
facilitating focal adhesions.
11.3.1
Aggrecan
The ACAN molecule (Figure 11.4) contains multiple functional domains. The
globular domains G1 and G2 are separated by a short interglobular domain, and
the G2 and G3 regions are separated by a long GAG attachment region which
consists of adjacent domains rich in KS and CS, but also possesses sites for the
attachment of
O
-linked oligosaccharides which with age may become substituted
with KS. The G1 region is at the N-terminus of the core protein, and can be further
subdivided in three functional domains termed A, B1 and B2. The aggregates are
composed of a central fi lament of hyaluronic acid with up to 100 ACAN molecules
radiating from it with each interaction able to be stabilized by the presence of a
link protein. ACANase (a member of the ADAMTS family - metalloproteinases
