Mayans O, Wuerges J, Canela S, Gautel M, Wilmanns M
EMBL Hamburg Outstation, Germany.
Structure. 2001 Apr 4;9(4):331-40. doi: 10.1016/s0969-2126(01)00591-3.
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.
The structure of the Ig domain I1 from the I band of titin has been determined to 2.1 A resolution. It reveals a novel, reversible disulphide bridge, which is neither required for correct folding nor changes the chemical stability of I1, 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.
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 I1 Ig domain with respect to each other when exposed to mechanical forces.
巨大的肌联蛋白通过连接肌节的Z盘和中央M线，对骨骼肌和心肌细胞中的细丝系统起作用。肌联蛋白的生理功能之一是在肌节中充当被动弹簧，这是通过其中央I带区域的弹性特性实现的。肌联蛋白包含约300个结构域，其中一半以上折叠成免疫球蛋白样（Ig）结构域。肌联蛋白I带的Ig结构域片段已被广泛用作研究蛋白质弹性分子基础的模板。
已确定肌联蛋白I带的Ig结构域I1的结构分辨率为2.1埃。它揭示了一种新型的可逆二硫键，该二硫键对于正确折叠既不是必需的，也不会改变I1的化学稳定性，但预计它在活性肌节中对肌联蛋白的弹性特性有机械贡献。在肌联蛋白最长同工型的92个Ig结构域中，至少有40个结构域有形成二硫键的潜力。
我们提出了一个模型，即在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肌联蛋白I带的弹性。在这个模型中，当暴露于机械力时，二硫键的形成可能会抑制I1 Ig结构域的两个β折叠或其他机械稳定实体相对于彼此的可能定向运动。
