Department of Cell and Molecular Biology, Northwestern University, Chicago, Illinois 60611, USA.
J Biol Chem. 2010 Mar 12;285(11):8155-62. doi: 10.1074/jbc.M109.068247. Epub 2010 Jan 12.
The kinesin-1 molecular motor contains an ATP-dependent microtubule-binding site in its N-terminal head domain and an ATP-independent microtubule-binding site in its C-terminal tail domain. Here we demonstrate that a kinesin-1 tail fragment associates with microtubules with submicromolar affinity. Binding is largely electrostatic in nature, and is facilitated by a region of basic amino acids in the tail and the acidic E-hook at the C terminus of tubulin. The tail binds to a site on tubulin that is independent of the head domain-binding site but overlaps with the binding site of the microtubule-associated protein Tau. Surprisingly, the kinesin tail domain stimulates microtubule assembly and stability in a manner similar to Tau. The biological function of this strong kinesin tail-microtubule interaction remains to be seen, but it is likely to play an important role in kinesin regulation due to the close proximity of the microtubule-binding region to the conserved regulatory and cargo-binding domains of the tail.
驱动蛋白-1 分子马达在其 N 端头部结构域含有一个依赖于 ATP 的微管结合位点，在其 C 端尾部结构域含有一个不依赖于 ATP 的微管结合位点。在这里，我们证明了驱动蛋白-1 的尾部片段以亚毫摩尔亲和力与微管结合。结合在很大程度上是静电性质的，并且受到尾部碱性氨基酸区域和微管蛋白 C 末端酸性 E 钩的促进。尾部结合到微管蛋白上的一个位点，该位点与头部结构域结合位点无关，但与微管相关蛋白 Tau 的结合位点重叠。令人惊讶的是，驱动蛋白尾部结构域以类似于 Tau 的方式刺激微管组装和稳定性。这种强驱动蛋白尾部-微管相互作用的生物学功能尚待观察，但由于微管结合区域与尾部保守的调节和货物结合结构域非常接近，因此它很可能在驱动蛋白调节中发挥重要作用。
