美国加州大学Ahmet Yildiz、Eva Nogales、Qianglin Fang课题组合作的最新研究揭示了微管 (MT) 相关蛋白 7 (MAP7)调控驱动蛋白1（kinesin-1）的结构和功能机制。相关论文于2022年1月21日发表于国际学术期刊《科学》杂志。

使用冷冻电镜和单分子成像，研究人员探究了MAP7如何结合MT并促进kinesin-1运动。MAP7的MT结合域(MTBD)与MT结合在原丝脊和横向接触位点之间形成了延伸的α螺旋。意外的是，MTBD与kinesin-1的结合位点部分重叠并抑制了其运动。然而，通过将kinesin-1拴在MT上，MAP7的投影域阻碍了电机解离，并促进了它与可接近相邻位点的结合。当MTs被MAP7饱和时，MTBD的抑制作用占主导地位。

该研究结果揭示了MAP7在与MT竞争性结合的情况下如何实现对kinesin-1进行双相调节。

据了解，MAP7是 kinesin-1开启细胞内货物运输所需的辅助因子。

附：英文原文

Title: Structural and functional insight into regulation of kinesin-1 by microtubule-associated protein MAP7

Author: Luke S. Ferro, Qianglin Fang, Lisa Eshun-Wilson, Jonathan Fernandes, Amanda Jack, Daniel P. Farrell, Mert Golcuk, Teun Huijben, Katelyn Costa, Mert Gur, Frank DiMaio, Eva Nogales, Ahmet Yildiz

Issue&Volume: 2022-01-21

Abstract: Microtubule (MT)–associated protein 7 (MAP7) is a required cofactor for kinesin-1–driven transport of intracellular cargoes. Using cryo–electron microscopy and single–molecule imaging, we investigated how MAP7 binds MTs and facilitates kinesin-1 motility. The MT-binding domain (MTBD) of MAP7 bound MTs as an extended α helix between the protofilament ridge and the site of lateral contact. Unexpectedly, the MTBD partially overlapped with the binding site of kinesin-1 and inhibited its motility. However, by tethering kinesin-1 to the MT, the projection domain of MAP7 prevented dissociation of the motor and facilitated its binding to available neighboring sites. The inhibitory effect of the MTBD dominated as MTs became saturated with MAP7. Our results reveal biphasic regulation of kinesin-1 by MAP7 in the context of their competitive binding to MTs.

DOI: abf6154

Source: https://www.science.org/doi/10.1126/science.abf6154