The crystal structure of the C-terminal fragment of striated-muscle α-tropomyosin reveals a key troponin T recognition site

Contraction in striated and cardiac muscles is regulated by the motions of a Ca(2+)-sensitive tropomyosin/troponin switch. In contrast, troponin is absent in other muscle types and in nonmuscle cells, and actomyosin regulation is myosin-linked. Here we report an unusual crystal structure at 2.7 Å of the C-terminal 31 residues of rat striated-muscle α-tropomyosin (preceded by a fragment of the GCN4 leucine zipper). The C-terminal 22 residues (263–284) of the structure do not form a two-stranded α-helical coiled coil as does the rest of the molecule, but here the α-helices splay apart and are stabilized by the formation of a tail-to-tail dimer with a symmetry-related molecule. The site of splaying involves a small group of destabilizing core residues that is present only in striated muscle tropomyosin isoforms. These results reveal a specific recognition site for troponin T and clarify the physical basis for the unique regulatory mechanism of striated muscles.