Functional role of the core gap in the middle part of tropomyosinстатья
Статья опубликована в высокорейтинговом журнале
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Дата последнего поиска статьи во внешних источниках: 30 августа 2018 г.
Аннотация:Tropomyosin (Tpm) is an a-helical coiled-coil actin-binding protein playing 4
an essential role in the regulation of muscle contraction. The middle part
of the Tpm molecule has some specific features, such as the presence of
noncanonical residues as well as a substantial gap at the interhelical interface,
which are believed to destabilize a coiled-coil and impart structural
flexibility to this part of the molecule. To study how the gap affects structural
and functional properties of a-striated Tpm (the Tpm1.1 isoform that
is expressed in cardiac and skeletal muscles) we replaced large conserved
apolar core residues located at both sides of the gap with smaller ones by 5
mutations M127A/I130A and M141A/Q144A. We found that in contrast
with the stabilizing substitutions D137L and G126R studied earlier, these
substitutions have no appreciable influence on thermal unfolding and
domain structure of the Tpm molecule. They also do not affect actin-binding
properties of Tpm. However, they strongly increase sliding velocity of
regulated actin filaments in an in vitro motility assay and cause an oversensitivity
of the velocity to Ca2+ similar to the stabilizing substitutions
D137L and G126R. Molecular dynamics shows that the substitutions studied
here increase bending stiffness of the coiled-coil structure of Tpm, like
that of G126R/D137L, probably due to closure of the interhelical gap in
the area of the substitutions. Our results clearly indicate that the conserved
middle part of Tpm is important for the fine tuning of the Ca2+ regulation
of actin–myosin interaction in muscle.