Deciphering the design of the tropomyosin molecule

The crystal structure at 2.0-Angstrom resolution of an 81-residue N-terminal fragment of muscle alpha -tropomyosin reveals a parallel two-stranded alpha -helical coiled-coil structure with a remarkable core, The high alanine content of the molecule is clustered into short regions where the local 2-fold symmetry is broken by a small (approximate to1.2-Angstrom) axial staggering of the helices, The joining of these regions with neighboring segments, where the helices are in axial register, gives rise to specific bends in the molecular axis. We observe such bends to be widely distributed in two-stranded alpha -helical coiled-coil proteins. This asymmetric design in a dimer of identical (or highly similar) sequences allows the tropomyosin molecule to adopt multiple bent conformations, The seven alanine clusters in the core of the complete molecule (which spans seven monomers of: the actin helix) promote the semiflexible winding of the tropomyosin filament necessary for its regulatory role in muscle contraction.