Chemistry Reference
In-Depth Information
thesis of the polymeric GAG chain and the enzymes involved are known, but the
fi eld is still in rapid evolution and there remain many challenges to study the
function and impact of PGs in development, biology and pathophysiology. The
tasks concern the knowledge of the three-dimensional conformation of the protein
core, the binding domains and affi nity of protein and GAG chain to different
counterparts, the function-dependent variation of GAG chain length, the degree
and location of sulfation, and the development of experimental animal models to
study PG functions and defi ciency diseases.
Summary Box
PGs comprise a collection of macromolecules that are composed of a protein
to which long unbranched GAG chains made of repeating disaccharide units
are covalently linked by posttranslational modifi cation. PGs are widespread in
the animal kingdom. PGs perform three major functions: (i) PGs are essential
constituents of an extracellular framework needed for structural organization
of all organs in multicellular organisms; (ii) PGs play a key role as storage depot
for cell membrane associated growth factors and cytokines and their bioactivity;
(iii) Transmembrane or GPI-anchored PGs act as coreceptors for growth
factors, as attachment sites for blood cells, matrix components and viruses, and
as modulators of enzyme activity. The cytosolic domain of transmembrane PGs
is involved in intracellular signaling.
References
1
7
Iozzo RV (Ed.),
Proteoglycans - Structure, Biol-
ogy, and Molecular Interactions
.
Sajdera SW , Hascall VC . Proteinpolysaccha-
ride complex from bovine nasal cartilage. A
comparison of low and high shear extraction
procedures .
J Biol Chem
1969 ; 244 : 77 - 87 .
Spicer AP
et al.
A hyaluronan binding link
protein gene family whose members are
physically linked adjacent to chondroitin sul-
fate proteoglycan core protein genes: the
missing links.
J Biol Chem
2003 ; 278 : 21083 -
91 .
Hascall VC
et al.
Intracellular hyaluronan: a
new frontier for infl ammation?
Biochim Bio-
phys Acta
2004 ; 1673 : 3 - 12 .
Bengtsson E
et al.
The primary structure of
a basic leucine-rich repeat protein, PRELP,
found in connective tissues.
J Biol Chem
1995 ; 270 : 25639 - 44 .
Iozzo RV . The biology of the small leucine -
rich proteoglycans. Functional network of
interactive proteins.
J Biol Chem
1999 ; 274 :
18843 - 6 .
Marcel
Dekker, New York , 2000 .
Ayad S
et al.
(Eds.),
The Extracellular Ma-
trix Facts Book
. Academic Press , London ,
1994 .
Iozzo RV . Basement membrane proteo-
glycans: from cellar to ceiling.
Nat Rev Mol
Cell Biol
2005 ; 6 : 646 - 56 .
Day AJ . The structure and regulation of
hyaluronan - binding proteins .
Biochem Soc
Trans
1999 ; 27 : 115 - 21 .
Hascall VC , Heinegard D . Aggregation of
cartilage proteoglycans. I. The role of hyal-
uronic acid.
J Biol Chem
1974 ; 249 : 4232 -
41 .
Iozzo RV , Murdoch AD . Proteoglycans of
the extracellular environment: clues from
the gene and protein side offer novel per-
spectives in molecular diversity and func-
tion .
FASEB J
1996 ; 10 : 598 - 614 .
2
8
3
4
9
5
10
6
11
