The crystal structure of the C-terminal fragment of striated-muscle α-tropomyosin reveals a key troponin T recognition site
The crystal structure of the C-terminal fragment of striated-muscle α-tropomyosin reveals a key troponin T recognition site
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DOI：
10.1073/pnas.102179999
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发表时间：
2002-05-28
影响因子：
11.1
通讯作者：
Cohen, C
中科院分区：
文献类型：
--
作者：
Li, Y;Mui, S;Cohen, C
横纹肌和心肌的收缩由对钙敏感的原肌球蛋白/肌钙蛋白开关的运动调节。相比之下，肌钙蛋白在其他肌肉类型和非肌肉细胞中都不存在，肌动肌球蛋白的调节与肌球蛋白有关。在这里，我们报告了一个不寻常的晶体结构，在大鼠横纹肌a-原肌球蛋白C-末端31个残基的2.7埃处(前面有一段Gcn4亮氨酸拉链)。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a-螺旋卷曲，但在这里，a-螺旋分开，并通过与对称相关分子形成尾到尾的二聚体来稳定。伸展部位涉及一小群不稳定的核心残基，仅存在于横纹肌原肌球蛋白亚型中。这些结果揭示了肌钙蛋白T的特定识别位点，并阐明了横纹肌独特调节机制的物理基础。
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 Angstrom of the C-terminal 31 residues of rat striated-muscle a-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 a-helical coiled coil as does the rest of the molecule, but here the a-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.