MAP2 and tau bind longitudinally along the outer ridges of microtubule protofilaments.
MAP2 and tau bind longitudinally along the outer ridges of microtubule protofilaments.
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Map2和Tau沿微管原丝的外脊纵向结合。
DOI：
10.1083/jcb.200201048
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发表时间：
2002-06-24
影响因子：
7.8
通讯作者：
Milligan, Ronald A
中科院分区：
文献类型：
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作者：
Al-Bassam, Jawdat;Ozer, Rachel S;Safer, Daniel;Halpain, Shelley;Milligan, Ronald A
MAP 2和tau表现出微管稳定活性，与神经元轴突和树突的发育和维持有关。这些蛋白质共有一个同源的COOH末端结构域，由三个或四个微管结合重复序列组成，这些重复序列被重复序列间（IR）隔开。为了研究MAP 2和tau如何稳定微管，我们使用cryo-EM和螺旋图像分析计算了完全用MAP 2c或tau装饰的微管的3D图。将这些图与未修饰的微管图进行比较，发现微管外部沿原丝脊的沿着密度增加，表明MAP 2c和tau在结合微管时形成有序结构。附着在MAP 2c的第二个IR上的11个金的定位表明IR也位于沿着脊，而不是在原丝之间。归因于微管相关蛋白的密度位于螺旋11和12以及微管蛋白的COOH末端附近。我们的数据进一步表明，在重复结构域中观察到的进化上维持的差异对于不同重复序列特异性靶向α或β微管蛋白可能是重要的。这些结果提供了强有力的证据表明，MAP 2c和tau稳定微管通过结合沿着个别原丝，可能通过桥接微管蛋白接口。
MAP2 and tau exhibit microtubule-stabilizing activities that are implicated in the development and maintenance of neuronal axons and dendrites. The proteins share a homologous COOH-terminal domain, composed of three or four microtubule binding repeats separated by inter-repeats (IRs). To investigate how MAP2 and tau stabilize microtubules, we calculated 3D maps of microtubules fully decorated with MAP2c or tau using cryo-EM and helical image analysis. Comparing these maps with an undecorated microtubule map revealed additional densities along protofilament ridges on the microtubule exterior, indicating that MAP2c and tau form an ordered structure when they bind microtubules. Localization of undecagold attached to the second IR of MAP2c showed that IRs also lie along the ridges, not between protofilaments. The densities attributable to the microtubule-associated proteins lie in close proximity to helices 11 and 12 and the COOH terminus of tubulin. Our data further suggest that the evolutionarily maintained differences observed in the repeat domain may be important for the specific targeting of different repeats to either α or β tubulin. These results provide strong evidence suggesting that MAP2c and tau stabilize microtubules by binding along individual protofilaments, possibly by bridging the tubulin interfaces.