Amos Linda A
MRC Laboratory of Molecular Biology, Hills Road, Cambridge, UKCB2 2QH.
Org Biomol Chem. 2004 Aug 7;2(15):2153-60. doi: 10.1039/b403634d. Epub 2004 Jul 14.
Microtubules are designed to be dynamically unstable. GTP hydrolysis converts an initially stable polymeric structure into an unstable one in which strain at the interfaces between longitudinal neighbours in the helical lattice of subunits is balanced by lateral interactions. However, stability can be modulated by a variety of factors, including associated proteins and a variety of drug molecules. Stabilising drugs such as Taxol and the assembly-promoting repeat motifs of tau protein occupy a special pocket in beta-tubulin. Microtubule destabilizing drugs such as colchicine alter the longitudinal interfaces of the subunits so that they cannot assemble into a microtubule lattice. These mechanisms are discussed in terms of the atomic structure of the protein.
微管被设计成具有动态不稳定性。GTP水解将最初稳定的聚合物结构转化为不稳定的结构，其中亚基螺旋晶格中纵向相邻分子间的应变通过横向相互作用得以平衡。然而，稳定性可由多种因素调节，包括相关蛋白和各种药物分子。诸如紫杉醇等稳定药物以及tau蛋白的组装促进重复基序占据β-微管蛋白中的一个特殊口袋。诸如秋水仙碱等微管去稳定药物会改变亚基的纵向界面，使其无法组装成微管晶格。将根据蛋白质的原子结构对这些机制进行讨论。
