Microtubule (MT)-associated proteins (MAPs) regulate intracellular transport by selectively recruiting or excluding kinesin and dynein motors from MTs. We used single-molecule and cryo-electron imaging to determine the mechanism of MAP-motor interactions in vitro. Unexpectedly, we found that the regulatory role of a MAP cannot be predicted based on whether it overlaps with the motor binding site or forms liquid condensates on the MT. Although the MT binding domain (MTBD) of MAP7 overlaps with the kinesin-1 binding site, tethering of kinesin-1 by the MAP7 projection domain supersedes this inhibition and results in biphasic regulation of kinesin-1 motility. Conversely, the MTBD of tau inhibits dynein motility without overlapping with the dynein binding site or by forming tau islands on the MT. Our results indicate that MAPs sort intracellular cargos moving in both directions, as neither dynein nor kinesin can walk on a MAP-coated MT without favorably interacting with that MAP.

中文翻译：

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微管相关蛋白抑制运动的机制

微管（MT）相关蛋白（MAP）通过选择性地从MT中募集或排除驱动蛋白和动力蛋白马达来调节细胞内运输。我们使用单分子和低温电子成像来确定MAP-电机相互作用的机制。出乎意料的是，我们发现无法基于MAP与电机结合位点重叠还是在MT上形成液体冷凝物来预测其调控作用。尽管MAP7的MT结合域（MTBD）与kinesin-1结合位点重叠，但是MAP7投影域对kinesin-1的束缚取代了这种抑制作用，并导致了对kinesin-1动力的双相调节。相反，tau的MTBD可抑制动力蛋白的运动，而不会与动力蛋白结合位点重叠或在MT上形成tau岛。