Li Yu, Mui Suet, Brown Jerry H, Strand James, Reshetnikova Ludmilla, Tobacman Larry S, Cohen Carolyn
Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, MA 02454-9110, USA.
Proc Natl Acad Sci U S A. 2002 May 28;99(11):7378-83. doi: 10.1073/pnas.102179999.
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.
横纹肌和心肌的收缩受钙敏感原肌球蛋白/肌钙蛋白开关运动的调节。相比之下，其他肌肉类型和非肌肉细胞中不存在肌钙蛋白，肌动球蛋白的调节是与肌球蛋白相关的。在此，我们报道了大鼠横纹肌α-原肌球蛋白C末端31个残基（前面是GCN4亮氨酸拉链的一个片段）在2.7埃分辨率下的异常晶体结构。该结构的C末端22个残基（263 - 284）不像分子的其余部分那样形成双链α-螺旋卷曲螺旋，而是α-螺旋展开，并通过与一个对称相关分子形成尾对尾二聚体而稳定。展开位点涉及一小群仅存在于横纹肌原肌球蛋白同工型中的不稳定核心残基。这些结果揭示了肌钙蛋白T的特异性识别位点，并阐明了横纹肌独特调节机制的物理基础。
