350
10 Proteins of Muscle and the Cytoskeleton
small mammals; they also occur at lower levels in
the brain and other non-muscle tissues of vertebrates. They are hardly detectable in the heart and
gut muscles [81,241]. The chicken thymus contains a peptide that induces T-cell markers on cultured bone-marrow cells and is referred to, therefore, as avian thymic hormone. The sequence
shows, however, that it is really a non-muscle
parvalbumin [26, 211]. The parvalbumins in
muscles have the function of a soluble relaxation
factor: the calcium released from the sarcoplasmic reticulum in excited muscle binds initially
to troponin C, thereby activating the actomyosin
ATPase and triggering contraction. Although parvalbumin has a higher calcium affinity than troponin C, the excess of magnesium in the relaxed
muscle results in it being fully loaded with magnesium, the dissociation of which requires a certain
time. The calcium pump of the sarcoplasmic reticulum has an affinity even higher than that of parvalbumin, but it must first be activated. Muscle
relaxation thus begins with the transfer of Ca 2 +
from troponin C to parvalbumin. After a certain
delay, calcium is returned to the sarcoplasmic reticulum by the calcium pump, and the Ca 2 + bound
to parvalbumin exchanges with Mg2+ due to the
declining Ca2+: Mg2+ ratio [238].
As the relaxation rate of a muscle is mainly
determined by the transfer of Ca2+ from troponin
C to parvalbumin, the rate should be correlated
to the parvalbumin concentration. In actual fact,
comparison of different muscle fibres in an animal shows the highest parvalbumin concentration
in type lIB (fast-twitch glycolytic), and in comparisons of the muscles of different mammalian species the highest values are found for the gastrocnemius of the mouse (4.9 g/kg) and the lowest
values for the muscles of man and the horse
(:::; 0.001 g/kg). The parvalbumin of rat brain and
testis is identical to that in muscle. In non-muscle
cells, parvalbumin may be involved in calcium
homeostasis as a calcium buffer. More than 20
parvalbumin sequences from mammals, reptiles,
amphibians, Crossopterygei and teleosts are
known, and indicate a relatively rapid evolution
(Table 10.1). Based on sequence characters and
the isoelectric point, two different types of parvalbumin are recognized (a and ~) and these can
occur together in the same muscle [81, 241].
Instead of parvalbumins, invertebrate muscles
contain sarcoplasmic calcium-binding proteins
(SCBPs) with very heterogeneous structures; they
have been reported, for example, from annelids,
crustaceans, mussels and lancelets. Alone in the
Crustacea, there are dimeric SCBPs with two 22kDa chains and altogether six calcium-binding
sites, four of which also competitively bind magnesium. In the decapods Astacus leptodactylus,
Homarus gammarus and Hippolyte zostericola,
two types of chain are found in different speciesspecific ratios, from which homo- and heterodimers with the same calcium-binding properties are
formed [116]. The SCBP of the scallop Patinopecten yessoensis has a length of 176 amino acids, corresponding to 20.1 kDa; of the four binding sites
present only I and III are functional. In the polychaete Nereis diversicolor and Perinereis vancaurica SeBPs, which are more-or-Iess the same size,
domain IV can also bind Ca 2 + bind Ca 2 + [279]. In
addition to calmodulin, the cilia of Tetrahymena
thermophila contain two further calcium-binding
proteins of 23 and 25 kDa, each with four EFhand domains [43,272]. The flagella of Trypanosoma cruzi and T. brucei have homologous
calcium-binding proteins of 23 kDa [161].
Four sequenced SCBPs isolated from amphioxus (Branchiostoma lanceolatum) differ in only
1-7 of their 185 amino acids; they bear four EFhand domains, of which I-III are functional
calcium-binding sites, and one of them also competitively binds magnesium [275]. Amphioxus
possesses a further calcium-binding protein of 161
amino acids with an acetylated N-terminus. The
C-terminal half of the molecule, with the two
functional calcium-binding domains III and IV,
agrees 45 % with human calmodulin and 40 %
with troponin C of rabbit skeletal muscle. The Nterminal half contains two non-functional Ca 2 +
domains and shows only 24 and 30 % similarity,
respectively, to the two mammalian proteins.
Because of its similarity to calmodulin, this protein is known as the calcium vector protein
(CaVP) [139]. It builds a complex with a target
protein (CaVPT) of 243 amino acids which can
interact with thick myofilaments via two immunoglobulin-like domains [274]. The direct transduction of Ca 2 + signals to an effector system has
also been described for the S-100 proteins, which
are widely distributed in the animal kingdom, and
for the spec proteins of the sea urchin. The S-lOO
proteins make up a family of small Ca2+ -binding
modulator proteins of 10-12 kDa; they were discovered in mammalian brain but have since been
reported in many different animals from protozoans to man. In the mammals, they are homo- or
heterodimers of a and ~ subunits, which show
about 50 % sequence difference to each other,
but contain two EF-hand domains each. They
bind to various effector proteins and are involved
in the process of cell differentiation and interac-
10 Proteins of Muscle and the Cytoskeleton
small mammals; they also occur at lower levels in
the brain and other non-muscle tissues of vertebrates. They are hardly detectable in the heart and
gut muscles [81,241]. The chicken thymus contains a peptide that induces T-cell markers on cultured bone-marrow cells and is referred to, therefore, as avian thymic hormone. The sequence
shows, however, that it is really a non-muscle
parvalbumin [26, 211]. The parvalbumins in
muscles have the function of a soluble relaxation
factor: the calcium released from the sarcoplasmic reticulum in excited muscle binds initially
to troponin C, thereby activating the actomyosin
ATPase and triggering contraction. Although parvalbumin has a higher calcium affinity than troponin C, the excess of magnesium in the relaxed
muscle results in it being fully loaded with magnesium, the dissociation of which requires a certain
time. The calcium pump of the sarcoplasmic reticulum has an affinity even higher than that of parvalbumin, but it must first be activated. Muscle
relaxation thus begins with the transfer of Ca 2 +
from troponin C to parvalbumin. After a certain
delay, calcium is returned to the sarcoplasmic reticulum by the calcium pump, and the Ca 2 + bound
to parvalbumin exchanges with Mg2+ due to the
declining Ca2+: Mg2+ ratio [238].
As the relaxation rate of a muscle is mainly
determined by the transfer of Ca2+ from troponin
C to parvalbumin, the rate should be correlated
to the parvalbumin concentration. In actual fact,
comparison of different muscle fibres in an animal shows the highest parvalbumin concentration
in type lIB (fast-twitch glycolytic), and in comparisons of the muscles of different mammalian species the highest values are found for the gastrocnemius of the mouse (4.9 g/kg) and the lowest
values for the muscles of man and the horse
(:::; 0.001 g/kg). The parvalbumin of rat brain and
testis is identical to that in muscle. In non-muscle
cells, parvalbumin may be involved in calcium
homeostasis as a calcium buffer. More than 20
parvalbumin sequences from mammals, reptiles,
amphibians, Crossopterygei and teleosts are
known, and indicate a relatively rapid evolution
(Table 10.1). Based on sequence characters and
the isoelectric point, two different types of parvalbumin are recognized (a and ~) and these can
occur together in the same muscle [81, 241].
Instead of parvalbumins, invertebrate muscles
contain sarcoplasmic calcium-binding proteins
(SCBPs) with very heterogeneous structures; they
have been reported, for example, from annelids,
crustaceans, mussels and lancelets. Alone in the
Crustacea, there are dimeric SCBPs with two 22kDa chains and altogether six calcium-binding
sites, four of which also competitively bind magnesium. In the decapods Astacus leptodactylus,
Homarus gammarus and Hippolyte zostericola,
two types of chain are found in different speciesspecific ratios, from which homo- and heterodimers with the same calcium-binding properties are
formed [116]. The SCBP of the scallop Patinopecten yessoensis has a length of 176 amino acids, corresponding to 20.1 kDa; of the four binding sites
present only I and III are functional. In the polychaete Nereis diversicolor and Perinereis vancaurica SeBPs, which are more-or-Iess the same size,
domain IV can also bind Ca 2 + bind Ca 2 + [279]. In
addition to calmodulin, the cilia of Tetrahymena
thermophila contain two further calcium-binding
proteins of 23 and 25 kDa, each with four EFhand domains [43,272]. The flagella of Trypanosoma cruzi and T. brucei have homologous
calcium-binding proteins of 23 kDa [161].
Four sequenced SCBPs isolated from amphioxus (Branchiostoma lanceolatum) differ in only
1-7 of their 185 amino acids; they bear four EFhand domains, of which I-III are functional
calcium-binding sites, and one of them also competitively binds magnesium [275]. Amphioxus
possesses a further calcium-binding protein of 161
amino acids with an acetylated N-terminus. The
C-terminal half of the molecule, with the two
functional calcium-binding domains III and IV,
agrees 45 % with human calmodulin and 40 %
with troponin C of rabbit skeletal muscle. The Nterminal half contains two non-functional Ca 2 +
domains and shows only 24 and 30 % similarity,
respectively, to the two mammalian proteins.
Because of its similarity to calmodulin, this protein is known as the calcium vector protein
(CaVP) [139]. It builds a complex with a target
protein (CaVPT) of 243 amino acids which can
interact with thick myofilaments via two immunoglobulin-like domains [274]. The direct transduction of Ca 2 + signals to an effector system has
also been described for the S-100 proteins, which
are widely distributed in the animal kingdom, and
for the spec proteins of the sea urchin. The S-lOO
proteins make up a family of small Ca2+ -binding
modulator proteins of 10-12 kDa; they were discovered in mammalian brain but have since been
reported in many different animals from protozoans to man. In the mammals, they are homo- or
heterodimers of a and ~ subunits, which show
about 50 % sequence difference to each other,
but contain two EF-hand domains each. They
bind to various effector proteins and are involved
in the process of cell differentiation and interac-