Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
Int J Mol Sci. 2021 Jul 15;22(14):7563. doi: 10.3390/ijms22147563.
Titin is a giant protein in the sarcomere that plays an essential role in muscle contraction with actin and myosin filaments. However, its utility goes beyond mechanical functions, extending to versatile and complex roles in sarcomere organization and maintenance, passive force, mechanosensing, and signaling. Titin's multiple functions are in part attributed to its large size and modular structures that interact with a myriad of protein partners. Among titin's domains, the N2A element is one of titin's unique segments that contributes to titin's functions in compliance, contraction, structural stability, and signaling via protein-protein interactions with actin filament, chaperones, stress-sensing proteins, and proteases. Considering the significance of N2A, this review highlights structural conformations of N2A, its predisposition for protein-protein interactions, and its multiple interacting protein partners that allow the modulation of titin's biological effects. Lastly, the nature of N2A for interactions with chaperones and proteases is included, presenting it as an important node that impacts titin's structural and functional integrity.
肌联蛋白是肌节中的一种巨大蛋白，在与肌动蛋白和肌球蛋白丝的相互作用中对肌肉收缩起着至关重要的作用。然而，它的用途不仅限于机械功能，还扩展到肌节组织和维持、被动力、机械感受和信号转导的多功能和复杂作用。肌联蛋白的多种功能部分归因于其庞大的尺寸和模块化结构，这些结构与无数的蛋白质伴侣相互作用。在肌联蛋白的结构域中，N2A 元件是肌联蛋白的独特片段之一，通过与肌动蛋白丝、伴侣蛋白、应激感应蛋白和蛋白酶的蛋白质-蛋白质相互作用，为肌联蛋白的顺应性、收缩、结构稳定性和信号转导功能做出贡献。鉴于 N2A 的重要性，本综述重点介绍了 N2A 的结构构象、其易于发生蛋白质-蛋白质相互作用的特性，以及其多个相互作用的蛋白质伴侣，这些都允许调节肌联蛋白的生物学效应。最后，还包括了 N2A 与伴侣蛋白和蛋白酶相互作用的性质，将其作为一个重要的节点，影响肌联蛋白的结构和功能完整性。
