Structural evidence for a possible role of reversible disulphide bridge formation in the elasticity of the muscle protein titin
Structural evidence for a possible role of reversible disulphide bridge formation in the elasticity of the muscle protein titin
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DOI：
10.1016/s0969-2126(01)00591-3
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发表时间：
2001-04-07
期刊：
影响因子：
5.7
通讯作者：
Wilmanns, M
中科院分区：
文献类型：
--
作者：
Mayans, O;Wuerges, J;Wilmanns, M
背景：巨型肌肉蛋白Titin通过连接肌节的Z盘和中央M线，参与骨骼肌和心肌细胞的微丝系统。肌动蛋白的生理功能之一是充当肌节的被动弹簧，这是通过其中央I带区的弹性性质实现的。Titin包含约300个结构域，其中一半以上折叠为免疫球蛋白样结构域(Ig)。肌动蛋白I带的Ig结构域片段已被广泛用于研究蛋白质弹性的分子基础。结果：确定了肌动蛋白I带的Ig结构域II的结构分辨率为2.1埃。它揭示了一种新的、可逆的二硫键，它既不是正确折叠所必需的，也不改变II的化学稳定性，但它被预测为在活动的肌瘤中对Titin的弹性性质有机械贡献。在最长的肌动蛋白亚型的92个Ig结构域中，至少有40个结构域有可能形成二硫键。结论：我们提出了一个模型，氧化应激条件下二硫键的形成可能通过增加肌节阻力来调节Titin中I带的弹性。在这个模型中，二硫键的形成可以阻止两个β片断或II Ig结构域的其他机械稳定实体在受到机械力时可能的定向运动。
Background: The giant muscle protein titin contributes to the filament system in skeletal and cardiac muscle cells by connecting the Z disk and the central M line of the sarcomere. One of the physiological functions of titin is to act as a passive spring in the sarcomere, which is achieved by the elastic properties of its central I band region. Titin contains about 300 domains of which more than half are folded as immunoglobulin-like (Ig) domains. Ig domain segments of the I band of titin have been extensively used as templates to investigate the molecular basis of protein elasticity.Results: The structure of the Ig domain II from the I band of titin has been determined to 2.1 Angstrom resolution. It reveals a novel, reversible disulphide bridge, which is neither required for correct folding nor changes the chemical stability of ii, but it is predicted to contribute mechanically to the elastic properties of titin in active sarcomeres. From the 92 Ig domains in the longest isoform of titin, at least 40 domains have a potential for disulphide bridge formation.Conclusions: We propose a model where the formation of disulphide bridges under oxidative stress conditions could regulate the elasticity of the I band in titin by increasing sarcomeric resistance. In this model, the formation of the disulphide bridge could refrain a possible directed motion of the two beta sheets or other mechanically stable entities of the II Ig domain with respect to each other when exposed to mechanical forces.