Chemistry Reference
In-Depth Information
been identifi ed. The structural diversity originates from alternative splicing pro-
cesses which generate four splice variants in humans (V0, V1, V2 and V3) with
molecular masses of 370, 262, 180 and 72 kDa. The number of CS attachment sites
varies from 17-23 (V0) and 12-15 (V1) to 5-8 (V2). Due to the absence of the
central GAG carrying domain V3 is devoid of CS side-chains and is therefore not
a PG. In the isoforms V0-V2 chondroitin 6-sulfate and chondroitin 4-sulfate are
found in a ratio of 2:1. Apart from HA, VCAN interacts with various ligands.
Binding is mediated by both the DS chains and the protein. In particular, the C-
terminal epidermal growth factor (EGF ) - like repeats, the C -type lectin domain and
the suchi element are altogether capable of binding
D
- Man,
D
- Gal,
L
- Fuc,
D
- GlcNAc,
HS, fi bronectin and collagen I. All these binding activities contribute to the high
organizational level of the extracellular matrix of all internal organs including
fi brous and elastic cartilage, tendon, skeletal muscle, and the dermis.
11.3.3
Neurocan, Brevican
The nervous tissue PG NCAN has a double-loop protein core for HA binding and
a C - terminal EGF - like and C -type lectin-type domain showing 60% homology to
those of ACAN and VCAN. The middle domain has no homology to any known
protein in adult, it has only one CS chain and a cleaved form of its core protein.
NCAN binds to neural cell adhesion molecules, and inhibits neural adhesion and
neurite outgrowth. Together with NCAN, BCAN is found in the brain, it is much
shorter and shows little homology to the other HA-binding PGs. A signifi cant
amount of BCAN is devoid of any GAG chains, indicating that BCAN is a 'part-
time' PG. In brain it is present predominantly in primary cerebellar astrocytes,
but not in neurons.
11.4
Small Leucine - Rich PG s
The small leucine-rich PGs (SLRPs) form a large family of leucine-rich repeat
proteins [10-13]. All SLRPs have 10-12 tandem repeats of 24 amino acids with
hydrophobic residues in conserved positions. The main members of the family
are decorin ( DCN ), biglycan ( BCN ), fi bromodulin ( FMOD ) and lumican ( LUM ).
They can be divided into several subfamilies based on their gene organization, the
number of leucine-rich repeats and the type of GAG chain substituent. The four
main SLRPs have 10 leucine-rich repeats which are fl anked by disulfi de - bonded
domains. DCN and BCN are classifi ed as DS PGs, whereas FMOD and LUM are
KS PGs. All SLRPs possess
N
-linked oligosaccharide chains within their central
leucine-rich repeats. The CS/DS attachment sites of DCN and BCN are within the
extreme N-terminus of their core protein. In DCN, one attachment site at amino
acid residue 4 is present; in BCN, two attachment sites at amino acid residues 5
and 10 are present. GAG-free forms of BCN, FMOD and LUM are the result of
