Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway, NJ 08854, USA.
J Struct Biol. 2010 May;170(2):319-24. doi: 10.1016/j.jsb.2009.12.013. Epub 2009 Dec 29.
Tropomyosin is a two-chained alpha-helical coiled coil that binds along the length of the actin filament and regulates its function. The paper addresses the question of how a "simple" coiled-coil sequence encodes the information for binding and regulating the actin filament, its universal target. Determination of the tropomyosin sequence confirmed Crick's predicted heptapeptide repeat of hydrophobic interface residues and revealed additional features that have been shown to be important for its function: a 7-fold periodicity predicted to correspond to actin binding sites and interruptions of the canonical interface with destabilizing residues, such as Ala. Evidence from published work is summarized, leading to the proposal of a paradigm that binding of tropomyosin to the actin filament requires local instability as well as regions of flexibility. The flexibility derives from bends and local unfolding at regions with a destabilized coiled-coil interface, as well as from the dynamic end-to-end complex. The features are required for tropomyosin to assume the form of the helical actin filament, and to bind to actin monomers along its length. The requirement of instability/flexibility for binding may be generalized to the binding of other coiled coils to their targets.
原肌球蛋白是一种由两条链组成的α-螺旋卷曲螺旋，沿着肌动蛋白丝的长度结合并调节其功能。本文探讨了一个“简单”的卷曲螺旋序列如何编码与肌动蛋白丝结合和调节的信息，肌动蛋白丝是其普遍的靶标。原肌球蛋白序列的确定证实了克里克预测的疏水面接口残基的七肽重复，并揭示了其他被证明对其功能很重要的特征：7 倍周期性预测与肌动蛋白结合位点相对应，以及与不稳定残基（如丙氨酸）的经典接口中断。总结了已发表工作的证据，提出了一个范例，即原肌球蛋白与肌动蛋白丝的结合需要局部不稳定性以及灵活性区域。这种灵活性源于具有不稳定卷曲螺旋界面的区域的弯曲和局部展开，以及动态的末端到末端的复合物。这些特征是原肌球蛋白形成螺旋肌动蛋白丝并沿着其长度与肌动蛋白单体结合所必需的。对于结合来说，不稳定性/灵活性的要求可能被推广到其他卷曲螺旋与其靶标的结合。
