Linke W A
Institute of Physiology II, University of Heidelberg, Germany.
Histol Histopathol. 2000 Jul;15(3):799-811. doi: 10.14670/HH-15.799.
Titin, the giant protein of striated muscle, provides a continuous link between the Z-disk and the M-line of a sarcomere. The elastic I-band section of titin comprises two main structural elements, stretches of immunoglobulin-like domains and a unique sequence, the PEVK segment. Both elements contribute to the extensibility and passive force development of nonactivated muscle. Extensibility of the titin segments in skeletal muscle has been determined by immunofluorescence/immunoelectron microscopy of sarcomeres stained with sequence-assigned titin antibodies. The force developed upon stretch of titin has been measured on isolated molecules or recombinant titin fragments with the help of optical tweezers and the atomic force microscope. Force has also been measured in single isolated myofibrils. The force-extension relation of titin could be readily fitted with models of biopolymer elasticity. For physiologically relevant extensions, the elasticity of the titin segments was largely explainable by an entropic-spring mechanism. The modelling explains why during stretch of titin, the Ig-domain regions (with folded modules) extend before the PEVK domain. In cardiac muscle, I-band titin is expressed in different isoforms, termed N2-A and N2-B. The N2-A isoform resembles that of skeletal muscle, whereas N2-B titin is shorter and is distinguished by cardiac-specific Ig-motifs and nonmodular sequences within the central I-band section. Examination of N2-B titin extensibility revealed that this isoform extends by recruiting three distinct elastic elements: poly-Ig regions and the PEVK domain at lower stretch and, in addition, a unique 572-residue sequence insertion at higher physiological stretch. Extension of all three elements allows cardiac titin to stretch fully reversibly at physiological sarcomere lengths, without the need to unfold individual Ig domains. However, unfolding of a very small number of Ig domains remains a possibility.
肌联蛋白是横纹肌中的一种巨大蛋白质，它在肌节的Z盘和M线之间提供了连续的连接。肌联蛋白的弹性I带部分包含两个主要结构元件，即免疫球蛋白样结构域的延伸段和一个独特序列，即PEVK片段。这两个元件都有助于非激活肌肉的伸展性和被动力的产生。通过用序列指定的肌联蛋白抗体染色的肌节的免疫荧光/免疫电子显微镜，已经确定了骨骼肌中肌联蛋白片段的伸展性。借助光镊和原子力显微镜，已经在分离的分子或重组肌联蛋白片段上测量了肌联蛋白拉伸时产生的力。也已经在单个分离的肌原纤维中测量了力。肌联蛋白的力-伸长关系很容易用生物聚合物弹性模型来拟合。对于生理相关的伸长，肌联蛋白片段的弹性在很大程度上可以用熵弹簧机制来解释。该模型解释了为什么在肌联蛋白拉伸过程中，Ig结构域区域（具有折叠模块）比PEVK结构域先伸展。在心肌中，I带肌联蛋白以不同的异构体形式表达，称为N2-A和N2-B。N2-A异构体类似于骨骼肌的异构体，而N2-B肌联蛋白较短，其特征在于中央I带部分中的心脏特异性Ig基序和非模块化序列。对N2-B肌联蛋白伸展性的研究表明，这种异构体通过募集三个不同的弹性元件来伸展：在较低拉伸时为多Ig区域和PEVK结构域，此外，在较高生理拉伸时为一个独特的572个残基的序列插入。所有这三个元件的伸展使得心肌肌联蛋白在生理肌节长度下能够完全可逆地伸展，而无需展开单个Ig结构域。然而，极少数Ig结构域展开的可能性仍然存在。
