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

doi:10.1073/pnas.102179999

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

^*Rosenstiel Basic Medical Sciences Research Center and ^†Biophysics and Structural Biology Program, Brandeis University, Waltham, MA 02454-9110; and ^§Departments of Internal Medicine and Biochemistry, University of Iowa, Iowa City, IA 52242

Contributed by Carolyn Cohen

Abstract

Contraction in striated and cardiac muscles is regulated by the motions of a Ca²⁺-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.

Footnotes

↵ ‡ This manuscript is dedicated to Suet Mui, who contributed greatly to this work, and who died on September 12, 2001, after a long illness.
↵ ¶ To whom reprint requests should be addressed. E-mail: ccohen{at}brandeis.edu.
Data Deposition: The atomic coordinates have been deposited in the Protein Data Bank, www.rcsb.org (PDB ID code 1kql).
↵ ‖ de Sousa, A. D. & Farah, C. S. (2001) Biophys. J. 80, 91a.
Abbreviations:

Tm,

tropomyosin;

TnT,

troponin T;

TnC,

troponin C;

TnI,

troponin I