Molecular basis of mRNA transport by a kinesin-1-atypical tropomyosin complex.
Molecular basis of mRNA transport by a kinesin-1-atypical tropomyosin complex.
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DOI：
10.1101/gad.348443.121
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发表时间：
2021-07-01
影响因子：
10.5
通讯作者：
Ephrussi A
中科院分区：
文献类型：
--
作者：
Dimitrova-Paternoga L;Jagtap PKA;Cyrklaff A;Vaishali;Lapouge K;Sehr P;Perez K;Heber S;Löw C;Hennig J;Ephrussi A
在这里，Dimitrova-Paternoga等人展示了Khc-aTm 1（果蝇驱动蛋白-1，也称为驱动蛋白重链[Khc]，与假定的货物接头，非典型原肌球蛋白[aTm 1]复合）的高分辨率晶体结构，其介导oskar mRNA转运到果蝇卵母细胞的后极。他们表明aTm 1结合到Khc上进化上保守的货物结合位点，证明Khc直接结合RNA，并表明aTm 1在Khc与RNA的相互作用中起稳定作用，这将aTm 1与经典的运动衔接子区分开来。驱动蛋白-1在细胞内长距离携带货物，包括蛋白质、RNA、囊泡和病原体。驱动蛋白的机械化学循环被很好地描述，但是它们如何建立货物特异性还没有完全理解。oskar mRNA运输到果蝇卵母细胞的后极由果蝇驱动蛋白-1（也称为驱动蛋白重链（Khc））和假定的货物适配器（非典型原肌球蛋白，aTm 1）介导。蛋白质如何在mRNA转运中合作尚不清楚。在这里，我们提出了高分辨率的晶体结构的Khc-aTm 1复合物。蛋白质形成三重卷曲螺旋，包括两个登记的Khc链和一个aTm 1链，在反平行方向。我们发现，aTm 1结合到一个进化上保守的货物结合位点上的Khc，和突变分析证实了这种相互作用的重要性，在体内的mRNA运输。此外，我们证明，Khc直接结合RNA，它这样做是通过其替代货物结合域，形成一个带正电荷的联合表面与aTm 1，以及通过其相邻的辅助微管结合域。最后，我们表明，aTm 1起着稳定的作用，在相互作用的Khc与RNA，区分aTm 1从经典的电机适配器。
Here, Dimitrova-Paternoga et al. present the high-resolution crystal structure of Khc–aTm1 (Drosophila kinesin-1, also called kinesin heavy chain [Khc], in complex with a putative cargo adaptor, the atypical tropomyosin [aTm1]), which mediates transport of oskar mRNA to the posterior pole of the Drosophila oocyte. They show that aTm1 binds to an evolutionarily conserved cargo binding site on Khc, demonstrate that Khc binds RNA directly, and show that aTm1 plays a stabilizing role in the interaction of Khc with RNA, which distinguishes aTm1 from classical motor adaptors. Kinesin-1 carries cargos including proteins, RNAs, vesicles, and pathogens over long distances within cells. The mechanochemical cycle of kinesins is well described, but how they establish cargo specificity is not fully understood. Transport of oskar mRNA to the posterior pole of the Drosophila oocyte is mediated by Drosophila kinesin-1, also called kinesin heavy chain (Khc), and a putative cargo adaptor, the atypical tropomyosin, aTm1. How the proteins cooperate in mRNA transport is unknown. Here, we present the high-resolution crystal structure of a Khc–aTm1 complex. The proteins form a tripartite coiled coil comprising two in-register Khc chains and one aTm1 chain, in antiparallel orientation. We show that aTm1 binds to an evolutionarily conserved cargo binding site on Khc, and mutational analysis confirms the importance of this interaction for mRNA transport in vivo. Furthermore, we demonstrate that Khc binds RNA directly and that it does so via its alternative cargo binding domain, which forms a positively charged joint surface with aTm1, as well as through its adjacent auxiliary microtubule binding domain. Finally, we show that aTm1 plays a stabilizing role in the interaction of Khc with RNA, which distinguishes aTm1 from classical motor adaptors.
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DOI：
10.1126/science.1204824
发表时间：
2011-08-12
期刊：
Science (New York, N.Y.)
影响因子：
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作者：
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DOI：
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发表时间：
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发表时间：
2014-07-21
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影响因子：
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作者：
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影响因子：
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Gaspar, Imre;Sysoev, Vasiliy;Ephrussi, Anne
通讯作者：
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