Intermediate filaments (IFs) are key players in multiple cellular processes throughout human tissues. Their biochemical and structural properties are important for understanding filament assembly mechanisms, for interactions between IFs and binding partners, and for developing pharmacological agents that target IFs. IF proteins share a conserved coiled-coil central-rod domain flanked by variable N-terminal ‘head’ and C-terminal ‘tail’ domains. There have been several recent advances in our understanding of IF structure from the study of keratins, glial fibrillary acidic protein, and lamin. These include discoveries of (i) a knob–pocket tetramer assembly mechanism in coil 1B; (ii) a lamin-specific coil 1B insert providing a one-half superhelix turn; (iii) helical, yet flexible, linkers within the rod domain; and (iv) the identification of coil 2B residues required for mature filament assembly. Furthermore, the head and tail domains of some IFs contain low-complexity aromatic-rich kinked segments, and structures of IFs with binding partners show electrostatic surfaces are a major contributor to complex formation. These new data advance the connection between IF structure, pathologic mutations, and clinical diseases in humans.

中间丝 (IF) 是整个人体组织中多个细胞过程的关键参与者。它们的生化和结构特性对于理解细丝组装机制、IFs 和结合伙伴之间的相互作用以及开发靶向 IFs 的药物非常重要。IF 蛋白共享一个保守的卷曲螺旋中心杆结构域，其两侧是可变的 N 端“头”和 C 端“尾”结构域。通过对角蛋白、胶质纤维酸性蛋白和核纤层蛋白的研究，我们对 IF 结构的理解取得了一些最新进展。其中包括发现 (i) 线圈 1B 中的旋钮-口袋四聚体组装机制；(ii) 薄片专用线圈 1B 插入件，提供半个超螺旋圈；(iii) 杆结构域内的螺旋但灵活的接头；(iv) 鉴定成熟灯丝组装所需的线圈 2B 残留物。此外，一些 IFs 的头部和尾部结构域包含低复杂度的富含芳香族的扭结片段，并且具有结合伙伴的 IFs 的结构表明静电表面是复合物形成的主要贡献者。这些新数据推动了人类 IF 结构、病理突变和临床疾病之间的联系。