Department of Molecular and Cellular Biology, University of California - Davis, 145 Briggs Hall, Davis, CA, 95616, USA.
Nat Commun. 2023 Aug 5;14(1):4715. doi: 10.1038/s41467-023-40425-4.
Microtubules are major components of the eukaryotic cytoskeleton. Posttranslational modifications (PTMs) of tubulin regulates interactions with microtubule-associated proteins (MAPs). One unique PTM is the cyclical removal and re-addition of the C-terminal tyrosine of α-tubulin and MAPs containing CAP-Gly domains specifically recognize tyrosinated microtubules. KIF13B, a long-distance transport kinesin, contains a conserved CAP-Gly domain, but the role of the CAP-Gly domain in KIF13B's motility along microtubules remains unknown. To address this, we investigate the interaction between KIF13B's CAP-Gly domain, and tyrosinated microtubules. We find that KIF13B's CAP-Gly domain influences the initial motor-microtubule interaction, as well as processive motility along microtubules. The effect of the CAP-Gly domain is enhanced when the motor domain is in the ADP state, suggesting an interplay between the N-terminal motor domain and C-terminal CAP-Gly domain. These results reveal that specialized kinesin tail domains play active roles in the initiation and continuation of motor movement.
微管是真核细胞骨架的主要组成部分。微管蛋白的翻译后修饰（PTMs）调节与微管相关蛋白（MAPs）的相互作用。一种独特的 PTM 是α-微管蛋白和含有 CAP-Gly 结构域的 MAPs 的 C 末端酪氨酸的周期性去除和重新添加，CAP-Gly 结构域特异性识别酪氨酸化的微管。KIF13B 是一种长距离运输驱动蛋白，含有保守的 CAP-Gly 结构域，但 CAP-Gly 结构域在 KIF13B 沿微管运动中的作用尚不清楚。为了解决这个问题，我们研究了 KIF13B 的 CAP-Gly 结构域与酪氨酸化微管之间的相互作用。我们发现 KIF13B 的 CAP-Gly 结构域影响初始的马达-微管相互作用，以及沿微管的进行性运动。当马达结构域处于 ADP 状态时，CAP-Gly 结构域的作用增强，这表明 N 端马达结构域和 C 端 CAP-Gly 结构域之间存在相互作用。这些结果表明，专门的驱动蛋白尾部结构域在马达运动的起始和延续中发挥积极作用。
