Müller Simone, Lange Stephan, Gautel Mathias, Wilmanns Matthias
EMBL Hamburg Outstation, c/o DESY, Notkestrasse 85, D-22603 Hamburg, Germany.
J Mol Biol. 2007 Aug 10;371(2):469-80. doi: 10.1016/j.jmb.2007.05.055. Epub 2007 May 25.
Most of the structure of the giant muscle protein titin is formed by small modular domains. Many of them are predicted to be arranged in repeats with short linkers that may be key determinants of the peculiar elastic properties of titin. Here, we present the molecular structure of a tandem arrangement of two immunoglobulin-like domains, A168 and A169, located within the A-band segment of titin. The two domains are connected by a 17 residue long beta-strand and form a common interface. Based on these data, we establish general principles to estimate the amount of conformational flexibility of tandem domain motifs in titin. An unusual bulge within the second domain, A169, is directly involved into binding to a sarcomeric ligand, MURF-1, thus suggesting a dual role of this tandem for both the mechanical properties of titin and for sarcomeric signaling.
巨大的肌肉蛋白肌联蛋白的大部分结构由小的模块化结构域组成。其中许多结构域预计以短连接子重复排列，这些连接子可能是肌联蛋白独特弹性特性的关键决定因素。在此，我们展示了位于肌联蛋白A带片段内的两个免疫球蛋白样结构域A168和A169的串联排列的分子结构。这两个结构域由一条17个残基长的β链连接，并形成一个共同界面。基于这些数据，我们建立了通用原则来估计肌联蛋白中串联结构域基序的构象灵活性。第二个结构域A169内的一个异常凸起直接参与与肌节配体MURF-1的结合，因此表明该串联结构对肌联蛋白的机械性能和肌节信号传导具有双重作用。
