Bennett P M, Gautel M
Randall Institute, King's College London, UK.
J Mol Biol. 1996 Jun 28;259(5):896-903. doi: 10.1006/jmbi.1996.0367.
Titin has been suggested to act as a molecular ruler for the precise assembly of thick filaments in vertebrate striated muscle. To investigate the correlation of titin domain patterns with the architecture of the thick filament at its end, we have investigated the axial position of titin epitopes at the thick-filament/I-band junction. Antibodies against immunoglobin (Ig) domains N and C-terminal to the unique block of six fibronectin-3 (fn3) domains in this region were used. The distance between these epitopes confirms the idea that titin is laid out linearly along the thick filament with each domain measuring about 4 nm in length. Our data demonstrate that the gap of myosin crossbridges near the end of the thick filament closely correlates with the stretch of six fn3 domains, and that the last two crossbridges are at the level of the first two groups of fn3 domains which were previously assigned to the I-band. We conclude that the pattern of groups of fn3 domains reflects the arrangement of the myosin heads, at least at the end of the A-band. It seems likely that an alteration in the interaction between myosin and the titin fn3 domains towards the end of the thick filament is important for the formation of the crossbridge gap and thus the termination of the thick filament.
肌联蛋白被认为在脊椎动物横纹肌中作为一种分子标尺，用于精确组装粗肌丝。为了研究肌联蛋白结构域模式与粗肌丝末端结构的相关性，我们研究了粗肌丝/ I带交界处肌联蛋白表位的轴向位置。使用了针对该区域六个纤连蛋白3（fn3）结构域独特模块N端和C端免疫球蛋白（Ig）结构域的抗体。这些表位之间的距离证实了肌联蛋白沿着粗肌丝呈线性排列的观点，每个结构域长度约为4 nm。我们的数据表明，粗肌丝末端附近肌球蛋白横桥的间隙与六个fn3结构域的伸展密切相关，并且最后两个横桥位于先前归属于I带的前两组fn3结构域的水平。我们得出结论，fn3结构域组的模式反映了肌球蛋白头部的排列，至少在A带末端是这样。在粗肌丝末端，肌球蛋白与肌联蛋白fn3结构域之间相互作用的改变似乎对于横桥间隙的形成以及粗肌丝的终止很重要。
