The crystal structure of the C-terminal fragment of striated-muscle alpha-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 A of the C-terminal 31 residues of rat striated-muscle alpha-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 alpha-helical coiled coil as does the rest of the molecule, but here the alpha-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.
Li
Yu
Y
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454-9110, USA.
Mui
Suet
S
Brown
Jerry H
JH
Strand
James
J
Reshetnikova
Ludmilla
L
Tobacman
Larry S
LS
Cohen
Carolyn
C
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000502:physiology*; D016297:Mutagenesis, Site-Directed; D010446:Peptide Fragments / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D020033:Protein Isoforms / Q000737:chemistry; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry; D014335:Tropomyosin / Q000737:chemistry* / Q000235:genetics; D020107:Troponin T / Q000737:chemistry / Q000378:metabolism*
D010446:Peptide Fragments; D020033:Protein Isoforms; D011994:Recombinant Proteins; D014335:Tropomyosin; D020107:Troponin T