Cohen Ariel, Ben-Nun Itai, Dharan Raviv, Tayri-Wilk Tamar, Shemesh Asaf, Ginsburg Avi, Millgram Abigail, Levi-Kalisman Yael, Ringel Israel, Raviv Uri
Institute of Chemistry, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
The Harvey M. Krueger Family Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem, Edmond J. Safra Campus, Givat Ram, Jerusalem 9190401, Israel.
ACS Appl Mater Interfaces. 2025 May 21;17(20):29146-29157. doi: 10.1021/acsami.5c01405. Epub 2025 May 12.
Structural transformations from ribbons to twisted ribbons to helical ribbons are often observed across supramolecular assemblies and macroscopic structures and can be described under a consistent theoretical framework. Conical molecular self-assembled structures, however, are rarely observed, may require more than one subunit, their dimensions are hard to control, and are poorly understood. Cytoskeleton microtubule (MT) is a dynamic protein-polymer that self-assembles from αβ-tubulin heterodimer, providing mechanical support to Eukaryotic cells. Colchicine is a drug known to bind the exchangeable nucleotide site on the β-tubulin subunit and suppress MT assembly. The tetravalent polyamine spermine promotes MT assembly and tubulin spiral structures, including conical tubulin spirals, tubules of conical spirals, and inverted helical tubules. Here we show how colchicine as a single agent suppressed MT and tubulin single ring assembly already at substoichiometric concentrations, whereas in the presence of spermine, the tubulin-colchicine stoichiometry controlled the dimensions and curvature of tubulin spiral assemblies. At a fixed spermine concentration, the concentration of colchicine modulated the radii of the nanotubular structures. The radii of the inverted helical nanotubules and conical spiral nanotubules monotonically decreased with colchicine concentration. We attribute our observation to the increased curvature of the tubulin dimer subunit induced by colchicine.
从带状结构到扭曲带状结构再到螺旋带状结构的结构转变，在超分子组装体和宏观结构中经常可以观察到，并且可以在一个统一的理论框架下进行描述。然而，锥形分子自组装结构很少被观察到，可能需要不止一个亚基，其尺寸难以控制，人们对其了解也很少。细胞骨架微管（MT）是一种由αβ-微管蛋白异二聚体自组装形成的动态蛋白质聚合物，为真核细胞提供机械支持。秋水仙碱是一种已知能结合β-微管蛋白亚基上可交换核苷酸位点并抑制微管组装的药物。四价多胺精胺促进微管组装和微管蛋白螺旋结构，包括锥形微管蛋白螺旋、锥形螺旋小管和反向螺旋小管。在这里，我们展示了秋水仙碱作为单一试剂，在亚化学计量浓度下就能抑制微管和微管蛋白单环组装，而在精胺存在的情况下，微管蛋白-秋水仙碱化学计量比控制着微管蛋白螺旋组装体的尺寸和曲率。在固定的精胺浓度下，秋水仙碱的浓度调节了纳米管结构的半径。反向螺旋纳米管和锥形螺旋纳米管的半径随秋水仙碱浓度的增加而单调减小。我们将我们的观察结果归因于秋水仙碱诱导的微管蛋白二聚体亚基曲率增加。
