blood plasma, in the rabbit they are identical,
apart from differences in the sugar residues
[119,201,271].
The polypeptide chains of all transferrins are
subdivided into two domains which agree in
37 -40 % of their sequences and each carry one
binding site. These binding sites consist of three
tyrosine and two histidine residues as well as an
HC03- ion bound electrostatically to an arginine
residue. The internal periodicity of the amino
acid sequence indicates that all transferrins arose
by the duplication of a short ancestral sequence;
this is recognizable from the spatial structure and
from the gene sequence [11, 119]. The sequences
of the two domains in human serum transferrin
and in chicken ovotransferrin have, in each case,
only about 40 % identical positions and thus differ to a greater extent than the homologous
domains of both proteins, which share 50 %
identity. Thus, the duplication of the ancestral
transferrin appears to have occurred before the
separation of the different types. The evolutionary advantage of the gene duplication may stem
from the failure of the kidneys to retain the
ancestral form of transferrin because of its low
molecular weight [271]. Comparative investigations of numerous fish, birds and mammals show
similar molecular masses of the serum transferrin
polypeptide chains, ranging from 61 to 87 kDa
[24]. Transferrin belongs to the proteins with a
high rate of evolution; the sequence agreement
between human and pig transferrin is 70 %, and
between human and Xenopus laevis is only 46 %
[15, 176]. The ovotransferrins and serum transferrins of all vertebrate classes show unusually high
variability. This is due in part to differences in the
carbohydrate fraction (sialic acid content) and in
part to allelic variation in the amino acid
sequence [47]. The polymorphism of the transferrins has often been exploited for studies of
population genetics.
Although the problem of Fe3+ transport also
exists for the invertebrates, little is known about
iron transport proteins. They have been detected,
for example, in the ascidian Pyura stolonifera, the
spider Dugesiella hentzi and the pocket crab Cancer magister. A haemolymph protein of 280 kDa,
isolated from the horseshoe crab Limulus polyphemus, consists of ten subunits each with two ironbinding sites. In the butterfly Manduca sexta an
80-kDa monomeric haemolymph protein containing one iron atom is present together with an ironrich protein of 490 kDa; this latter protein has subunits of 24 and 26 kDa and is very similar structurally and functionally to ferritin [16, 111, 258].
5.3.2 Haptoglobin and Haemopexin
189
5.3.2 Haptoglobin and Haemopexin
Haptoglobins (Hp) are az-glycoproteins which
bind in a ratio of 1: 1 to the haemoglobin released
from disintegrated erythrocytes. The whole
haptoglobin-haemoglobin complex is taken up
and metabolized by cells of the reticuloendothelial system; the haptoglobin molecules
are not recycled. Haptoglobins are widely distributed in mammals and birds but have not yet been
definitely identified in amphibians. In the urodeIan Taricha granulosa, the haemoglobin in haemolysed blood binds to albumin. Whilst a dramatic increase in az-glycoproteins, including haptoglobin, can be induced in higher vertebrates by,
for example, the injection of turpentine, this
acute-phase reaction is absent from Taricha [77].
The haptoglobin molecule is a tetramer with
two types of subunit bound by disulphide bridges:
smaller a-chains of 9 or 17 kDa and larger, glycosylated ~-chains of 40 kDa. Canine Hp lacks the
disulphide bridges between the dimers and the
rabbit Hp molecule has no disulphide bridges;
therefore, in SDS or urea the canine Hp splits
into dimers and the rabbit Hp into single chains
[136]. There are three allelic variants of the
human a-chain, one of which is increased in
length from 83 to 142 amino acids [152]. In the
neighbourhood of the human hp gene there is a
related gene, hpr (hp-related), which contains a
retroviral element in the first intron. Anthropoids
and Old World apes have three hp genes (hp, hpr,
hpp) but New World apes have only one. There is
also a retroviral element in the first intron of the
chimpanzee hpr gene and a further one in the
spacer between hpr and hpp. The triplication of
the hp gene apparently occurred after the separation of the apes of the Old World and the New
World; in humans, a gene was lost during unequal
crossing-over between hpr and hpp [162].
The amino acid sequence of the human haptoglobin ~-chain has ca. 30 % agreement with different serine proteases (see Fig. 3.6, p. 91). There
is 10-20 % difference between the N-terminal
sequence of the human haptoglobin ~-chain and
those of various other mammals. Immunologically, the haptoglobins of different Artiodactyla
show strong mutual cross-reactivity but only weak
interaction with human Hp; thus, haptoglobin
shows a medium rate of evolution similar to that
of haemoglobin. Chicken haptoglobin is very different, both structurally and functionally, from
that of mammals; full sequence analysis is needed
in order to determine whether it belongs to the
same protein super-family: it is a 68-kpa mono-
apart from differences in the sugar residues
[119,201,271].
The polypeptide chains of all transferrins are
subdivided into two domains which agree in
37 -40 % of their sequences and each carry one
binding site. These binding sites consist of three
tyrosine and two histidine residues as well as an
HC03- ion bound electrostatically to an arginine
residue. The internal periodicity of the amino
acid sequence indicates that all transferrins arose
by the duplication of a short ancestral sequence;
this is recognizable from the spatial structure and
from the gene sequence [11, 119]. The sequences
of the two domains in human serum transferrin
and in chicken ovotransferrin have, in each case,
only about 40 % identical positions and thus differ to a greater extent than the homologous
domains of both proteins, which share 50 %
identity. Thus, the duplication of the ancestral
transferrin appears to have occurred before the
separation of the different types. The evolutionary advantage of the gene duplication may stem
from the failure of the kidneys to retain the
ancestral form of transferrin because of its low
molecular weight [271]. Comparative investigations of numerous fish, birds and mammals show
similar molecular masses of the serum transferrin
polypeptide chains, ranging from 61 to 87 kDa
[24]. Transferrin belongs to the proteins with a
high rate of evolution; the sequence agreement
between human and pig transferrin is 70 %, and
between human and Xenopus laevis is only 46 %
[15, 176]. The ovotransferrins and serum transferrins of all vertebrate classes show unusually high
variability. This is due in part to differences in the
carbohydrate fraction (sialic acid content) and in
part to allelic variation in the amino acid
sequence [47]. The polymorphism of the transferrins has often been exploited for studies of
population genetics.
Although the problem of Fe3+ transport also
exists for the invertebrates, little is known about
iron transport proteins. They have been detected,
for example, in the ascidian Pyura stolonifera, the
spider Dugesiella hentzi and the pocket crab Cancer magister. A haemolymph protein of 280 kDa,
isolated from the horseshoe crab Limulus polyphemus, consists of ten subunits each with two ironbinding sites. In the butterfly Manduca sexta an
80-kDa monomeric haemolymph protein containing one iron atom is present together with an ironrich protein of 490 kDa; this latter protein has subunits of 24 and 26 kDa and is very similar structurally and functionally to ferritin [16, 111, 258].
5.3.2 Haptoglobin and Haemopexin
189
5.3.2 Haptoglobin and Haemopexin
Haptoglobins (Hp) are az-glycoproteins which
bind in a ratio of 1: 1 to the haemoglobin released
from disintegrated erythrocytes. The whole
haptoglobin-haemoglobin complex is taken up
and metabolized by cells of the reticuloendothelial system; the haptoglobin molecules
are not recycled. Haptoglobins are widely distributed in mammals and birds but have not yet been
definitely identified in amphibians. In the urodeIan Taricha granulosa, the haemoglobin in haemolysed blood binds to albumin. Whilst a dramatic increase in az-glycoproteins, including haptoglobin, can be induced in higher vertebrates by,
for example, the injection of turpentine, this
acute-phase reaction is absent from Taricha [77].
The haptoglobin molecule is a tetramer with
two types of subunit bound by disulphide bridges:
smaller a-chains of 9 or 17 kDa and larger, glycosylated ~-chains of 40 kDa. Canine Hp lacks the
disulphide bridges between the dimers and the
rabbit Hp molecule has no disulphide bridges;
therefore, in SDS or urea the canine Hp splits
into dimers and the rabbit Hp into single chains
[136]. There are three allelic variants of the
human a-chain, one of which is increased in
length from 83 to 142 amino acids [152]. In the
neighbourhood of the human hp gene there is a
related gene, hpr (hp-related), which contains a
retroviral element in the first intron. Anthropoids
and Old World apes have three hp genes (hp, hpr,
hpp) but New World apes have only one. There is
also a retroviral element in the first intron of the
chimpanzee hpr gene and a further one in the
spacer between hpr and hpp. The triplication of
the hp gene apparently occurred after the separation of the apes of the Old World and the New
World; in humans, a gene was lost during unequal
crossing-over between hpr and hpp [162].
The amino acid sequence of the human haptoglobin ~-chain has ca. 30 % agreement with different serine proteases (see Fig. 3.6, p. 91). There
is 10-20 % difference between the N-terminal
sequence of the human haptoglobin ~-chain and
those of various other mammals. Immunologically, the haptoglobins of different Artiodactyla
show strong mutual cross-reactivity but only weak
interaction with human Hp; thus, haptoglobin
shows a medium rate of evolution similar to that
of haemoglobin. Chicken haptoglobin is very different, both structurally and functionally, from
that of mammals; full sequence analysis is needed
in order to determine whether it belongs to the
same protein super-family: it is a 68-kpa mono-