The study investigates the 3D structure of vimentin intermediate filaments (VIFs), which are integral components of the cytoskeleton, providing cells with tissue-specific mechanical properties and participating in various cellular processes. Using cryo-focused ion-beam milling, cryo-electron microscopy, and tomography, the researchers obtained a detailed 3D structure of VIFs. They found that VIFs assemble into a modular, intertwined, and flexible helical structure composed of five protofibrils, each containing 40 α-helices in cross-section. Surprisingly, the intrinsically disordered head domains form a fiber in the lumen of VIFs, while the intrinsically disordered tails form lateral connections between the protofibrils. This discovery highlights how protein domains of low sequence complexity can complement well-folded protein domains to construct a biopolymer with significant mechanical strength and stretchability. The findings provide insights into the unique utilization of low-complexity domains in VIFs and other intermediate filaments, contributing to a better understanding of their role in cell mechanics and disease.The study investigates the 3D structure of vimentin intermediate filaments (VIFs), which are integral components of the cytoskeleton, providing cells with tissue-specific mechanical properties and participating in various cellular processes. Using cryo-focused ion-beam milling, cryo-electron microscopy, and tomography, the researchers obtained a detailed 3D structure of VIFs. They found that VIFs assemble into a modular, intertwined, and flexible helical structure composed of five protofibrils, each containing 40 α-helices in cross-section. Surprisingly, the intrinsically disordered head domains form a fiber in the lumen of VIFs, while the intrinsically disordered tails form lateral connections between the protofibrils. This discovery highlights how protein domains of low sequence complexity can complement well-folded protein domains to construct a biopolymer with significant mechanical strength and stretchability. The findings provide insights into the unique utilization of low-complexity domains in VIFs and other intermediate filaments, contributing to a better understanding of their role in cell mechanics and disease.