Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Blvd. Dallas, Texas 75390-9152, USA.
Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Blvd. Dallas, Texas 75390-9152, USA; Institute for Quantum Life Science, National Institutes for Quantum Science and Technology (QST), 4-9-1, Anagawa, Inage-ku, Chiba, 263-8555, Japan.
Curr Opin Cell Biol. 2023 Dec;85:102262. doi: 10.1016/j.ceb.2023.102262. Epub 2023 Oct 21.
The dominant structural feature of intermediate filament (IF) proteins is a centrally located α-helix. These long α-helical segments become paired in a parallel orientation to form coiled-coil dimers. Pairs of dimers further coalesce in an anti-parallel orientation to form tetramers. These early stages of intermediate filament assembly can be accomplished solely by the central α-helices. By contrast, the assembly of tetramers into mature intermediate filaments is reliant upon an N-terminal head domain. IF head domains measure roughly 100 amino acids in length and have long been understood to exist in a state of structural disorder. Here, we describe experiments favoring the unexpected idea that head domains self-associate to form transient structural order in the form of labile cross-β interactions. We propose that this weak form of protein structure allows for dynamic regulation of IF assembly and disassembly. We further offer that what we have learned from studies of IF head domains may represent a simple, unifying template for understanding how thousands of other intrinsically disordered proteins help to establish dynamic morphological order within eukaryotic cells.
中间丝（IF）蛋白的主要结构特征是中央存在α-螺旋。这些长的α-螺旋片段以平行的方向配对形成卷曲螺旋二聚体。二聚体进一步以反平行的方向聚集形成四聚体。中间丝组装的这些早期阶段仅可以通过中央α-螺旋完成。相比之下，四聚体组装成成熟的中间丝依赖于 N 端头部结构域。IF 头部结构域的长度约为 100 个氨基酸，长期以来人们一直认为它处于结构无序的状态。在这里，我们描述了一些实验，这些实验支持了一个出人意料的观点，即头部结构域通过自组装形成以不稳定的交叉β相互作用为形式的短暂结构有序。我们提出，这种弱蛋白结构形式允许中间丝组装和去组装的动态调节。我们进一步提出，我们从 IF 头部结构域研究中学到的东西可能代表了一个简单、统一的模板，用于理解数以千计的其他内在无序蛋白如何帮助在真核细胞内建立动态形态结构有序性。
