细胞生物学研究表明,原丝数量,微管的一个基本特征,可以与不同的微管蛋白同种型的表达相关。然而,不知道微管蛋白同种型是否直接控制这种基本的微管性质。这里,我们报告了纯化的人α1B/β3和α1B/β2B微管的高分辨率低温EM重建(3.5-3.65µ),并发现β-微管蛋白同种型可以确定原丝数量。13和14原丝微管的原子模型的比较揭示了微管蛋白亚基的可塑性,表现为“手风琴样”的分布式结构变化,可以容纳不同的晶格组织。此外,与α1B/β3微管相比,α1B/β2B长丝对MCAK或chTOG的被动分解和解聚更稳定,具有不同作用机制的微管相关蛋白。以不同比例混合微管蛋白同种型会产生微管,其原丝数量和稳定性介于同种型纯细丝之间。一起,我们的发现表明,微管原丝的数量和稳定性可以通过β-微管蛋白同种型组成来控制。
Cell biological studies have shown that protofilament number, a fundamental feature of microtubules, can correlate with the expression of different tubulin isotypes. However, it is not known if tubulin isotypes directly control this basic microtubule property. Here, we report high-resolution cryo-EM reconstructions (3.5-3.65 Å) of purified human α1B/β3 and α1B/β2B microtubules and find that the β-tubulin isotype can determine protofilament number. Comparisons of atomic models of 13- and 14-protofilament microtubules reveal how tubulin subunit plasticity, manifested in \"accordion-like\" distributed structural changes, can accommodate distinct lattice organizations. Furthermore, compared to α1B/β3 microtubules, α1B/β2B filaments are more stable to passive disassembly and against depolymerization by MCAK or chTOG, microtubule-associated proteins with distinct mechanisms of action. Mixing tubulin isotypes in different proportions results in microtubules with protofilament numbers and stabilities intermediate to those of isotypically pure filaments. Together, our findings indicate that microtubule protofilament number and stability can be controlled through β-tubulin isotype composition.