Goll C M, Pastore A, Nilges M
EMBL Meyerhofstrasse 1, 69117, Heidelberg, Germany Institut de Biologie Structurale J-P Ebel 41 Avenue des Martyrs, 38027 Grenoble, France.
Structure. 1998 Oct 15;6(10):1291-302. doi: 10.1016/s0969-2126(98)00129-4.
Titin is a huge protein ( approximately 3 MDa) that is present in the contractile unit (sarcomere) of striated muscle and has a key role in muscle assembly and elasticity. Titin is mainly composed of two types of module (type I and II). Type I modules are found exclusively in the region of titin localised in the A band, where they are arranged in a super-repeat pattern that correlates with the ultrastructure of the thick filament. No structure of a titin type I module has been reported so far.
We have determined the structure of a representative type I module, A71, using nuclear magnetic resonance (NMR) spectroscopy. The structure has the predicted fibronectin type III fold. Titin-specific conserved residues are either located at the putative module-module interfaces or along one side of the protein surface. Several proline residues that contribute to two stretches in a polyproline II helix conformation are solvent-exposed and line up as a continuous ribbon extending over more than two-thirds of the module surface. Homology models of the type I module N-terminal to A71 (A70) and the double module A70-A71 were used to discuss possible intermodule interactions and their role in module-module orientation.
As residues at the module-module interfaces are highly conserved, we speculate that similar interactions govern all of the interfaces between type I modules in titin. This conservation would lead to a regular multiple array of similar surface structures. Such an arrangement would allow arrays of contiguous type I modules to expose multiple proline stretches in a highly regular way and these may act as binding sites for other thick filament proteins.
肌联蛋白是一种巨大的蛋白质（约3兆道尔顿），存在于横纹肌的收缩单元（肌节）中，在肌肉组装和弹性方面发挥关键作用。肌联蛋白主要由两种类型的模块（I型和II型）组成。I型模块仅存在于肌联蛋白位于A带的区域，它们以与粗肌丝超微结构相关的超级重复模式排列。迄今为止，尚未报道过肌联蛋白I型模块的结构。
我们利用核磁共振（NMR）光谱法确定了一个代表性I型模块A71的结构。该结构具有预测的纤连蛋白III型折叠。肌联蛋白特异性保守残基要么位于假定的模块 - 模块界面处，要么沿着蛋白质表面的一侧。几个有助于形成两段多聚脯氨酸II螺旋构象的脯氨酸残基暴露于溶剂中，并排列成一条连续的带，延伸超过模块表面的三分之二。利用A71 N端的I型模块（A70）和双模块A70 - A71的同源模型来讨论可能存在的模块间相互作用及其在模块 - 模块定向中的作用。
由于模块 - 模块界面处的残基高度保守，我们推测类似的相互作用控制着肌联蛋白中所有I型模块之间的界面。这种保守性将导致形成规则的多个类似表面结构的阵列。这样的排列将使相邻I型模块的阵列以高度规则的方式暴露多个脯氨酸延伸段，这些延伸段可能充当其他粗肌丝蛋白的结合位点。
