but can also form the two different homodimers.
Each gene produces several tropomyosin isoforms, the exact number of which is not known,
even in the case of the common laboratory mammals. Mammals also express the a form of the
fast-twitch skeletal-muscle fibres in the heart,
whereas birds have heart-specific isoforms. Different isoforms are also found in non-muscle
cells. The production of isoforms by the ~-TM
gene of chicken is a good example of alternative
splicing; at least nine different mRNAs are produced by the use of two promoters and alternative splicing of several of the 13 exons. The
mRNAs of all muscle tropomyosins include exons
1-5 (amino acids 1-188) and 8-9 (amino acids
214-257), whereas exon 6 (amino acids 189-213)
and exon 11 (amino acids 258-284) are found
only in smooth-muscle mRNA, and the analogous exons 7 and 10 exist only in skeletal muscle.
An additional exon, 1', between exons 2 and 3
encodes, together with exons 3, 4, 5, 6A, 7,8 and
9A, a non-muscle-cell tropomyosin of 247 amino
acids [72, 166]. The species-specific and isoformspecific differences between the tropomyosins
involve 15-25 % of the whole sequence but are
mainly located at the C-terminal end. This region
is responsible for dimer formation and the binding of actin and troponin, and the tropomyosin
isoforms thus show considerable differences in
these properties.
Multiple tropomyosins are also known from
Drosophila. There are at least three musclespecific isoforms, of which two are encoded by the
same gene, Tml. Differential splicing of exon 4
leads to two muscle-type-specific isoforms with a
length of 284 amino acids, which differ only in 27
C-terminal amino acids. The third muscle-specific
tropomyosin is encoded by the gene Tm2 and, as
the result of a substitution in the stop codon, has
a length of 285 amino acids. Alternative splicing
produces a further non-muscle-cell tropomyosin
isoform from the same gene with a length of
252 amino acids [92]. A tropomyosin from the
locust Locusta migratoria agrees by 51-55 % in its
sequence of 283 amino acids with various vertebrate tropomyosins, and by 87 and 64 % with Tml
and Tm2 from Drosophila, respectively [148].
Tissue-specific tropomyosin isoforms have also
been found in other invertebrates, e.g. there are
up to five in various mussels, and two in the
muscles of the earthworm Lumbricus terrestris.
There are at least six tropomyosin isoforms in the
xiphosuran Tachypleus tridentatus, but these are
distributed equally in all tissues, i.e. tissue specificity is not so marked in this case [114, 187].
10.6 Tropomyosins and Troponins
345
The troponin complex consists of three noncovalently linked proteins: Tn-T as the
tropomyosin-binding component; Tn-I, which
inhibits actomyosin ATPase; and the calciumbinding Tn-C. All three types from the fast-twitch
skeletal-muscle fibres of rabbit have been
sequenced, and they constitute the most studied
model of the relationship between structure and
function in the troponin complexes. The Nterminal amino acids 1-70 of Tn-T bind in an antiparallel fashion to the C-terminus of one tropomyosin molecule and to several N-terminal amino
acids of the subsequent molecule. The C-terminal
region of the Tn-T binds to a second site, which is
20 nm from the first site, on the tropomyosin molecule. The contact sites between Tn-T and the
components Tn-C and Tn-I also lie in this region.
Binding of Ca2+ to Tn-C disrupts the binding of
Tn-T to the second site on the tropomyosin molecule and causes a conformational change which
expose the attachment site of the myosin head on
actin. In addition to that in the vertebrates, a
complete troponin complex has been found in several invertebrates, e.g. arthropods, molluscs and
the roundworm Ascaris lumbricoides [130]. Some
non-muscle cells contain only Tn-C, and as it cannot be involved in A regulation in the absence of
Tn-I and Tn-T, its function in this case is not clear.
The Tn-T from the muscles of the rabbit, rat
and chicken have very different lengths of
between 259 and 301 amino acids; Tn-T is, as a
rule, longer in arthropods and mussels than in the
vertebrates. Thus, in Tn-T evolution there have
been insertions and deletions of larger DNA segments as well as nucleotide substitutions [25]. Isoforms of Tn-T have been detected in vertebrates
of all classes and even in the ascidian Halocynthia
roretzi [206]. Like other muscle proteins, the troponins of the vertebrates show large differences
in different muscle types. Thus, in mammals and
birds, there are different isoforms of Tn-Tin heart
muscle and in fast-and-slow-twitch skeletal
muscle, and these are encoded by different genes.
There are also pseudogenes in the Tn-T gene
family. The number of isoforms of all tissuespecific Tn-Ts can be further increased by alternative splicing. In the fast-twitch skeletal-muscle
fibres of the rat, 64 Tn-T isoforms arise by the
alternative use of exons 4-8 and 16-17 [25]; the
situation is very similar for the Tn-T variants in
chicken skeletal muscle [249]. In the case of the
heart-specific Tn-T gene of the chicken, only one
of the two mRNAs formed receives the transcript
of exon 5 and is translated to the 301-amino-acid
isoform I of Tn-T, which predominates in the
Each gene produces several tropomyosin isoforms, the exact number of which is not known,
even in the case of the common laboratory mammals. Mammals also express the a form of the
fast-twitch skeletal-muscle fibres in the heart,
whereas birds have heart-specific isoforms. Different isoforms are also found in non-muscle
cells. The production of isoforms by the ~-TM
gene of chicken is a good example of alternative
splicing; at least nine different mRNAs are produced by the use of two promoters and alternative splicing of several of the 13 exons. The
mRNAs of all muscle tropomyosins include exons
1-5 (amino acids 1-188) and 8-9 (amino acids
214-257), whereas exon 6 (amino acids 189-213)
and exon 11 (amino acids 258-284) are found
only in smooth-muscle mRNA, and the analogous exons 7 and 10 exist only in skeletal muscle.
An additional exon, 1', between exons 2 and 3
encodes, together with exons 3, 4, 5, 6A, 7,8 and
9A, a non-muscle-cell tropomyosin of 247 amino
acids [72, 166]. The species-specific and isoformspecific differences between the tropomyosins
involve 15-25 % of the whole sequence but are
mainly located at the C-terminal end. This region
is responsible for dimer formation and the binding of actin and troponin, and the tropomyosin
isoforms thus show considerable differences in
these properties.
Multiple tropomyosins are also known from
Drosophila. There are at least three musclespecific isoforms, of which two are encoded by the
same gene, Tml. Differential splicing of exon 4
leads to two muscle-type-specific isoforms with a
length of 284 amino acids, which differ only in 27
C-terminal amino acids. The third muscle-specific
tropomyosin is encoded by the gene Tm2 and, as
the result of a substitution in the stop codon, has
a length of 285 amino acids. Alternative splicing
produces a further non-muscle-cell tropomyosin
isoform from the same gene with a length of
252 amino acids [92]. A tropomyosin from the
locust Locusta migratoria agrees by 51-55 % in its
sequence of 283 amino acids with various vertebrate tropomyosins, and by 87 and 64 % with Tml
and Tm2 from Drosophila, respectively [148].
Tissue-specific tropomyosin isoforms have also
been found in other invertebrates, e.g. there are
up to five in various mussels, and two in the
muscles of the earthworm Lumbricus terrestris.
There are at least six tropomyosin isoforms in the
xiphosuran Tachypleus tridentatus, but these are
distributed equally in all tissues, i.e. tissue specificity is not so marked in this case [114, 187].
10.6 Tropomyosins and Troponins
345
The troponin complex consists of three noncovalently linked proteins: Tn-T as the
tropomyosin-binding component; Tn-I, which
inhibits actomyosin ATPase; and the calciumbinding Tn-C. All three types from the fast-twitch
skeletal-muscle fibres of rabbit have been
sequenced, and they constitute the most studied
model of the relationship between structure and
function in the troponin complexes. The Nterminal amino acids 1-70 of Tn-T bind in an antiparallel fashion to the C-terminus of one tropomyosin molecule and to several N-terminal amino
acids of the subsequent molecule. The C-terminal
region of the Tn-T binds to a second site, which is
20 nm from the first site, on the tropomyosin molecule. The contact sites between Tn-T and the
components Tn-C and Tn-I also lie in this region.
Binding of Ca2+ to Tn-C disrupts the binding of
Tn-T to the second site on the tropomyosin molecule and causes a conformational change which
expose the attachment site of the myosin head on
actin. In addition to that in the vertebrates, a
complete troponin complex has been found in several invertebrates, e.g. arthropods, molluscs and
the roundworm Ascaris lumbricoides [130]. Some
non-muscle cells contain only Tn-C, and as it cannot be involved in A regulation in the absence of
Tn-I and Tn-T, its function in this case is not clear.
The Tn-T from the muscles of the rabbit, rat
and chicken have very different lengths of
between 259 and 301 amino acids; Tn-T is, as a
rule, longer in arthropods and mussels than in the
vertebrates. Thus, in Tn-T evolution there have
been insertions and deletions of larger DNA segments as well as nucleotide substitutions [25]. Isoforms of Tn-T have been detected in vertebrates
of all classes and even in the ascidian Halocynthia
roretzi [206]. Like other muscle proteins, the troponins of the vertebrates show large differences
in different muscle types. Thus, in mammals and
birds, there are different isoforms of Tn-Tin heart
muscle and in fast-and-slow-twitch skeletal
muscle, and these are encoded by different genes.
There are also pseudogenes in the Tn-T gene
family. The number of isoforms of all tissuespecific Tn-Ts can be further increased by alternative splicing. In the fast-twitch skeletal-muscle
fibres of the rat, 64 Tn-T isoforms arise by the
alternative use of exons 4-8 and 16-17 [25]; the
situation is very similar for the Tn-T variants in
chicken skeletal muscle [249]. In the case of the
heart-specific Tn-T gene of the chicken, only one
of the two mRNAs formed receives the transcript
of exon 5 and is translated to the 301-amino-acid
isoform I of Tn-T, which predominates in the