ABSTRACT
This review concerns the structure and functions of tropomyosin (TM), an actin-binding protein that plays a key role in the regulation of muscle contraction. The TM molecule is a dimer of α-helices, which form a coiled-coil. Recent views on the TM structure are analyzed, and special attention is concentrated on those structural traits of the TM molecule that distinguish it from the other coiled-coil proteins. Modern data are presented on TM functional properties, such as its interaction with actin and ability to move on the surface of actin filaments, which underlies the regulation of the actin-myosin interaction upon contraction of skeletal and cardiac muscles. Also, part of the review is devoted to analysis of the effects of mutations in TM genes associated with muscle diseases (myopathies) on the structure and functions of TM.
Subject(s)
Tropomyosin/chemistry , Actin Cytoskeleton/metabolism , Animals , Humans , Muscle Contraction , Muscles/chemistry , Muscles/metabolism , Muscles/physiology , Organ Specificity , Protein Binding , Protein Conformation , Protein Isoforms/chemistry , Protein Isoforms/metabolism , Protein Isoforms/physiology , Protein Stability , Tropomyosin/metabolism , Tropomyosin/physiologyABSTRACT
The mutation Arg91Gly (R91G) in beta-tropomyosin (beta-TM) is known to cause distal arthrogryposis, a severe congenital disorder of muscle tissues. To elucidate how this mutation affects the structural properties of beta-TM, the thermal unfolding of beta-TM carrying mutation Arg91Gly was compared with that of the wild type protein. It was shown by differential scanning calorimetry and circular dichroism that this point mutation dramatically decreases the thermal stability of a significant part of beta-TM (about a half of the molecule). This part of the beta-TM molecule carrying mutation R91G unfolds at approximately 28 degrees C, i.e., at a much lower temperature than the other part of the molecule, which unfolds at approximately 40 degrees C. Based on the comparison of the data obtained by differential scanning calorimetry with measurements of temperature dependence of pyrene excimer fluorescence, whose decrease reflects the dissociation of two beta-TM chains in the region of pyrene-labeled Cys-36, this thermal transition was assigned to the N-terminal part of beta-TM. Interestingly, the destabilizing effect of the mutation spreads along the coiled-coil assuming a high extent of cooperativity within this part of the beta-TM molecule.
