Chapter

Regulatory Mechanisms of Striated Muscle Contraction

Volume 592 of the series Advances in Experimental Medicine and Biology pp 137-151

Crystal Structures of Tropomyosin: Flexible Coiled-Coil

  • Yasushi NitanaiAffiliated withERATO Actin Filament Dynamics Project, JSTLaboratory for Structural Biochemistry, RIKEN SPring-8 Center
  • , Shiho MinakataAffiliated withERATO Actin Filament Dynamics Project, JST
  • , Kayo MaedaAffiliated withERATO Actin Filament Dynamics Project, JST
  • , Naoko OdaAffiliated withERATO Actin Filament Dynamics Project, JST
  • , Yuichiro MaédaAffiliated withERATO Actin Filament Dynamics Project, JSTLaboratory for Structural Biochemistry, RIKEN SPring-8 CenterDivision of Biological Science, Graduate School of Science, Nagoya University

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13.1. Abstruct

Tropomyosin (Tm) is a 400 Å long coiled coil protein, and with troponin it regulates contraction in skeletal and cardiac muscles in a [Ca2+]-dependent manner. Tm consists of multiple domains with diverse stabilities in the coiled coil form, thus providing Tm with dynamic flexibility. This flexibility must play important roles in the actin binding and the cooperative transition between the calcium regulated states of the entire muscle thin filament. In order to understand the flexibility of Tm in its entirety, the atomic coordinates of Tm are needed. Here we report the two crystal structures of Tm segments. One is rabbit skeletal muscle α-Tm encompassing residues 176–284 with an N-terminal extension of 25 residues from the leucine zipper sequence of GCN4, which includes the region that interacts with the troponin core domain. The other is α-Tm encompassing residues 176–273 with N- and C-terminal extensions of the leucine zipper sequences. These two crystal structures imply that this molecule is a flexible coiled coil. First, Tm’s are not homogeneous and smooth coiled coils, but instead they undulate, with highly fluctuating local parameters specifying the coiled coil. Independent fluctuating showed by two crystal structures is important. Second, in the first crystal, the coiled coil is bent by 9 degrees in the region centered about Y214-E218-Y221, where the inter-helical distance has its maximum. On the other hand, no bend is observed at the same region in the second crystal even if its inter-helical distance has also its maximum. E218, an unusual negatively charged residue at the a position in the heptad repeat, seems to play the key role in destabilizing the coiled coil with alanine destabilizing clusters.