The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size.
The number of Z-repeats and super-repeats in nebulin greatly varies across vertebrates and scales with animal size.
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DOI：
10.1085/jgp.202012783
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发表时间：
2021-03-01
期刊：
影响因子：
--
通讯作者：
Granzier H
中科院分区：
文献类型：
--
作者：
Gohlke J;Tonino P;Lindqvist J;Smith JE;Granzier H
戈尔克等人比较了53个物种中肌节蛋白伴肌动蛋白的结构。他们发现伴肌动蛋白结构重复单元的数量与动物体型之间存在关联，这对肌肉力学有影响。
伴肌动蛋白是一种骨骼肌蛋白，与肌节细肌丝相关联，在调节细肌丝长度和Z盘结构方面具有功能。在此我们研究了53种鸟类、鱼类、两栖动物、爬行动物和哺乳动物中的伴肌动蛋白基因。在所有物种中，伴肌动蛋白具有相似的结构域组成，主要由约30个氨基酸的模块（或简单重复单元）组成，每个模块都包含一个肌动蛋白结合位点。所有物种都有一个大的区域，其中简单重复单元被组织成七个模块的超重复单元，每个超重复单元都包含一个原肌球蛋白结合位点。超重复单元的数量在物种间存在很大差异，从21个（斑马鱼、蜂鸟）到31个（骆驼、黑猩猩）不等，而且重要的是，与体型成比例。大型动物中较高数量的超重复单元被证明会增加细肌丝长度，这有望增加肌节长度以实现最佳的力量产生，提高等长收缩力量产生的能量效率，并降低肌肉的缩短速度。自1950年A.V.希尔的研究以来，人们就知道随着物种体型增大，其肌肉的缩短速度会降低，而目前的研究表明伴肌动蛋白对这一机制基础有贡献。最后，我们分析了伴肌动蛋白C末端差异剪接的简单重复单元，其包含情况与Z盘的宽度相关。Z重复单元的数量差异很大（从5到18个），并且与超重复单元的数量相关。我们提出，大型动物中Z盘宽度的增加会在Z盘长时间受力时增加伴肌动蛋白与结构性Z盘蛋白之间的接触数量。
Gohlke et al. compare the structure of the sarcomeric protein nebulin across 53 species. They uncover an association between the number of nebulin structural repeats and animal body size that has implications for muscle mechanics. Nebulin is a skeletal muscle protein that associates with the sarcomeric thin filaments and has functions in regulating the length of the thin filament and the structure of the Z-disk. Here we investigated the nebulin gene in 53 species of birds, fish, amphibians, reptiles, and mammals. In all species, nebulin has a similar domain composition that mostly consists of ∼30-residue modules (or simple repeats), each containing an actin-binding site. All species have a large region where simple repeats are organized into seven-module super-repeats, each containing a tropomyosin binding site. The number of super-repeats shows high interspecies variation, ranging from 21 (zebrafish, hummingbird) to 31 (camel, chimpanzee), and, importantly, scales with body size. The higher number of super-repeats in large animals was shown to increase thin filament length, which is expected to increase the sarcomere length for optimal force production, increase the energy efficiency of isometric force production, and lower the shortening velocity of muscle. It has been known since the work of A.V. Hill in 1950 that as species increase in size, the shortening velocity of their muscle is reduced, and the present work shows that nebulin contributes to the mechanistic basis. Finally, we analyzed the differentially spliced simple repeats in nebulin's C terminus, whose inclusion correlates with the width of the Z-disk. The number of Z-repeats greatly varies (from 5 to 18) and correlates with the number of super-repeats. We propose that the resulting increase in the width of the Z-disk in large animals increases the number of contacts between nebulin and structural Z-disk proteins when the Z-disk is stressed for long durations.
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DOI：
10.1038/nrm3510
发表时间：
2013-02
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
13.6
作者：
Kiss B;Gohlke J;Tonino P;Hourani Z;Kolb J;Strom J;Alekhina O;Smith JE 3rd;Ottenheijm C;Gregorio C;Granzier H
通讯作者：
Granzier H
DOI：
10.1073/pnas.1804726115
发表时间：
2018-10-09
影响因子：
11.1
作者：
Kiss B;Lee EJ;Ma W;Li FW;Tonino P;Mijailovich SM;Irving TC;Granzier HL
通讯作者：
Granzier HL
影响因子：
9.9
作者：
Colombo, Irene;Scoto, Mariacristina;Muntoni, Francesco
通讯作者：
Muntoni, Francesco
影响因子：
5.6
作者：
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