section 10.3
Cell-Surface Glycoproteins
in the attachment of chondrocytes to collagen. A family
of cell surface adhesion receptor proteins known as
binds with fibronectin. Integrins are a fam-
ily of proteins containing «/3 heterodimers and pos-
sess receptors not only for fibronectin but for collagens,
laminin, fibrinogen, vitronectin, and integral membrane
protein of the immunoglobulin superfamily (Chapter 35).
A sequence of 3 amino acids (RGD) in fibronectin
is a recognition site for binding with integrin. Other
amino acid sequences that are present in proteins for
integrin recognition include KQAGDV, DGEA, EILDV,
and GPRP.
Red Blood Cell Membrane and
Membrane Skeleton Proteins
A major integral membrane glycoprotein of human red
blood cells,
glycophorin A,
has been characterized. It has
a molecular weight of 31,000. Each membrane contains
about 400,000 molecules of glycophorin, accounting for
about 1.5% of the weight of the membrane, while the car-
bohydrate portion constitutes about 40% of the weight.
The polypeptide consists of 131 amino acid residues
(Figure 10-11). The transmembrane protein has three dis-
tinct domains: a hydrophilic amino terminal end that
extends outside the membrane and contains all of the
oligosaccharide side chains; a hydrophobic middle region
buried in the lipid bilayer; and a hydrophilic region rich
in charged residues that protrudes into the cytosol. Gly-
cophorin A has 16 oligosaccharide units, of which 15
are linked by O-glycosidic bonds to serine or threonine
residues and one is linked by an N-glycosidic bond.
All of the O-linked oligosaccharides have the following
S ia -a (2
- *
6)-G al-/?(1 -> 3 U
J ^ G a lN A c-O -S er/T h r
where Sia = sialic acid, Gal = galactose, GalNAc = N-
acetylgalactose, and Ser/Thr = serine/threonine.
The N-linked oligosaccharide contains mannose. All
of the oligosaccharide chains appear in the 50 residues
of the amino terminal domain, in which amino acid
residues 2^4 and 10-15 all carry an oligosaccharide
unit in O-glycosidic linkage. The middle hydropho-
bic domain is believed to have an «-helical structure.
Glycophorin contains antigenic determinants for blood
groups M and N (see below). The M and N anti-
genic determinants are present on glycophorin A and
glycophorin B, respectively. The former differs from
the latter at positions 1 and 5 of the amino terminal
Glycophorin A
Glycophorin B
Glycophorin A is present in type M, glycophorin B in
type N, and both glycophorins in type MN individuals.
Antibodies directed against M and N do not cross-react
and can distinguish sequence differences between the two
glycophorins. Although some antibody preparations may
FIGURE 10-11
Primary structure of glycophorin A. There are 15 O-linked and 1 N-linked carbohydrates attached to the protein.
[Adapted from L. W. Stryer,
B io ch em istry,
3rd ed. W. H. Freeman, New York, 1995.]
previous page 193 Bhagavan Medical Biochemistry 2001 read online next page 195 Bhagavan Medical Biochemistry 2001 read online Home Toggle text on/off