The N2A region of titin has a unique structural configuration.
The N2A region of titin has a unique structural configuration.
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titin的N2A区具有独特的结构构型。
DOI：
10.1085/jgp.202012766
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发表时间：
2021-07-05
期刊：
影响因子：
--
通讯作者：
Fleming JR
中科院分区：
文献类型：
--
作者：
Stronczek C;Lange S;Bullard B;Wolniak S;Börgeson E;Mayans O;Fleming JR
Stronczek等人分析肌联蛋白-N2 A多聚Ig片段的结构，肌节中的关键信号元件。他们揭示了I81-I83串联的独特拓扑结构，但他们不能证实I81-I83中存在Ca 2+结合位点或N2 A与肌动蛋白的相互作用。肌联蛋白的N2 A片段是肌节I带中的主要信号中枢，其募集各种信号因子和加工酶。它也被认为是通过其与肌动蛋白的钙离子调节的关联在力的产生中发挥作用。然而，N2 A在重复和广泛的肌联蛋白链中选择性地执行这些功能的分子基础仍然知之甚少。在这里，我们分析了N2 A组分的结构及其与F-肌动蛋白的结合。具体而言，我们通过使用X射线晶体学阐明I81-I83串联的原子结构并计算I80的同源模型来表征其IG结构域的结构。结构数据显示这些结构域呈现异质和发散的IG折叠，其中I81和I83具有独特的环结构。值得注意的是，I81-I83串联体具有独特的旋转链排列，赋予其独特的多结构域形貌。然而，我们无法识别这些IG结构域中的特异性Ca 2+结合位点，也没有证据表明转染的C2 C12成肌细胞或C2 C12衍生的肌管中肌联蛋白N2 A组分与F-肌动蛋白相关。此外，F-肌动蛋白共沉降试验未能揭示N2 A的结合。我们的结论是，N2 A有一个独特的架构，可预见的支持其选择性招聘的结合伙伴的信号，但它的机械作用，通过与F-肌动蛋白的相互作用有待验证。
Stronczek et al. analyze the structure of the titin-N2A poly-Ig segment, a key signaling element in the sarcomere. They reveal a unique topography for the I81-I83 tandem, but they could not confirm the presence of Ca2+ binding sites in I81-I83 or the interaction of N2A with actin. The N2A segment of titin is a main signaling hub in the sarcomeric I-band that recruits various signaling factors and processing enzymes. It has also been proposed to play a role in force production through its Ca2+-regulated association with actin. However, the molecular basis by which N2A performs these functions selectively within the repetitive and extensive titin chain remains poorly understood. Here, we analyze the structure of N2A components and their association with F-actin. Specifically, we characterized the structure of its Ig domains by elucidating the atomic structure of the I81-I83 tandem using x-ray crystallography and computing a homology model for I80. Structural data revealed these domains to present heterogeneous and divergent Ig folds, where I81 and I83 have unique loop structures. Notably, the I81-I83 tandem has a distinct rotational chain arrangement that confers it a unique multi-domain topography. However, we could not identify specific Ca2+-binding sites in these Ig domains, nor evidence of the association of titin N2A components with F-actin in transfected C2C12 myoblasts or C2C12-derived myotubes. In addition, F-actin cosedimentation assays failed to reveal binding to N2A. We conclude that N2A has a unique architecture that predictably supports its selective recruitment of binding partners in signaling, but that its mechanical role through interaction with F-actin awaits validation.
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影响因子：
14.8
作者：
Kelley LA;Mezulis S;Yates CM;Wass MN;Sternberg MJ
通讯作者：
Sternberg MJ
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
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通讯作者：
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作者：
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通讯作者：
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影响因子：
3.5
作者：
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通讯作者：
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影响因子：
4
作者：
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通讯作者：
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