Domain swap in the C‐terminal ubiquitin‐like domain of human doublecortin

Rufer Arne C.; Kusznir Eric; Burger DominiqueStihle MartineRuf ArminRudolph Markus G.

首页> 外文期刊>Acta crystallographica. Section D, Structural biology. >Domain swap in the C‐terminal ubiquitin‐like domain of human doublecortin

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Domain swap in the C‐terminal ubiquitin‐like domain of human doublecortin

机译：域交换C检测终端泛素的类域的人类doublecortin

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Doublecortin, a microtubule‐associated protein that is only produced during neurogenesis, cooperatively binds to microtubules and stimulates microtubule polymerization and cross‐linking by unknown mechanisms. A domain swap is observed in the crystal structure of the C‐terminal domain of doublecortin. As determined by analytical ultracentrifugation, an open conformation is also present in solution. At higher concentrations, higher‐order oligomers of the domain are formed. The domain swap and additional interfaces observed in the crystal lattice can explain the formation of doublecortin tetramers or multimers, in line with the analytical ultracentrifugation data. Taken together, the domain swap offers a mechanism for the observed cooperative binding of doublecortin to microtubules. Doublecortin‐induced cross‐linking of microtubules can be explained by the same mechanism. The effect of several mutations leading to lissencephaly and double‐cortex syndrome can be traced to the domain swap and the proposed self‐association of doublecortin.

机译：Doublecortin、一个微管相关蛋白这只是产生在神经发生,合作与微管结合促进微管聚合和交叉连接通过未知的机制。交换是观察到的晶体结构C终端doublecortin领域。通过分析超速离心法、开放构象也出现在解决方案。寡聚物的浓度更高,更高的优先秩序域形成。额外的接口中观察到晶体晶格能解释doublecortin的形成四聚体或多聚体,符合数据分析超速离心法。在一起,域交换提供了一种机制观察到的合作doublecortin绑定微管。交叉连接微管可以解释的相同的机制。突变导致lissencephaly和双皮质综合征可以追溯到域交换和提出自己的协会doublecortin。

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《Acta crystallographica. Section D, Structural biology.》 |2018年第5期|450-462|共12页
作者
Rufer Arne C.; Kusznir Eric; Burger DominiqueStihle MartineRuf ArminRudolph Markus G.;
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pRED, Therapeutic Modalities, F. Hoffmann-La Roche, 4070Basel, Switzerland;

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正文语种英语
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关键词
Lissencephaly; Microtubules; doublecortinUltracentrifugationSwapDomain;

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Domain swap in the C‐terminal ubiquitin‐like domain of human doublecortin

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