Pajares María A, Pérez-Sala Dolores
Department of Structural and Chemical Biology, Centro de Investigaciones Biológicas Margarita Salas, C.S.I.C., Ramiro de Maeztu, 9, 28040 Madrid, Spain.
Biochem Soc Trans. 2024 Apr 24;52(2):849-860. doi: 10.1042/BST20231059.
Intermediate filaments (IFs) are cytoskeletal elements involved in mechanotransduction and in the integration of cellular responses. They are versatile structures and their assembly and organization are finely tuned by posttranslational modifications. Among them, type III IFs, mainly vimentin, have been identified as targets of multiple oxidative and electrophilic modifications. A characteristic of most type III IF proteins is the presence in their sequence of a single, conserved cysteine residue (C328 in vimentin), that is a hot spot for these modifications and appears to play a key role in the ability of the filament network to respond to oxidative stress. Current structural models and experimental evidence indicate that this cysteine residue may occupy a strategic position in the filaments in such a way that perturbations at this site, due to chemical modification or mutation, impact filament assembly or organization in a structure-dependent manner. Cysteine-dependent regulation of vimentin can be modulated by interaction with divalent cations, such as zinc, and by pH. Importantly, vimentin remodeling induced by C328 modification may affect its interaction with cellular organelles, as well as the cross-talk between cytoskeletal networks, as seems to be the case for the reorganization of actin filaments in response to oxidants and electrophiles. In summary, the evidence herein reviewed delineates a complex interplay in which type III IFs emerge both as targets and modulators of redox signaling.
中间丝（IFs）是参与机械转导和细胞反应整合的细胞骨架成分。它们是多功能结构，其组装和组织通过翻译后修饰进行精细调节。其中，III型中间丝，主要是波形蛋白，已被确定为多种氧化和亲电修饰的靶点。大多数III型中间丝蛋白的一个特征是其序列中存在单个保守的半胱氨酸残基（波形蛋白中的C328），这是这些修饰的热点，似乎在丝状网络应对氧化应激的能力中起关键作用。目前的结构模型和实验证据表明，这个半胱氨酸残基可能在丝中占据一个关键位置，使得由于化学修饰或突变导致的该位点的扰动，以结构依赖的方式影响丝的组装或组织。波形蛋白的半胱氨酸依赖性调节可通过与二价阳离子（如锌）的相互作用以及pH值进行调节。重要的是，由C328修饰诱导的波形蛋白重塑可能会影响其与细胞器的相互作用，以及细胞骨架网络之间的相互作用，就像氧化应激和亲电试剂作用下肌动蛋白丝的重组情况一样。总之，本文综述的证据描绘了一种复杂的相互作用，其中III型中间丝既是氧化还原信号的靶点，也是调节因子。
