Structural basis for cargo binding and autoinhibition of Bicaudal-D1 by a parallel coiled-coil with homotypic registry.
Structural basis for cargo binding and autoinhibition of Bicaudal-D1 by a parallel coiled-coil with homotypic registry.
复制标题
通过具有同型登记的平行卷曲线圈对 Bicaudal-D1 进行货物结合和自动抑制的结构基础。
DOI：
10.1016/j.bbrc.2015.03.054
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Wakamatsu K.
中科院分区：
文献类型：
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作者：
Terawaki S;Yoshikane A;Higuchi Y;Wakamatsu K.
Bicaudal-d1(Bicd1)是一种α螺旋卷曲蛋白，介导特定的货物与细胞质动力蛋白的结合。它在微管负端定向的细胞内转运中起着至关重要的作用。BICD 1的第三个C末端卷曲区域(BICD 1 CC3)在货物分拣中起重要作用，包括与小GTP酶Rab6和核孔复合体RAN结合蛋白2(RanBP2)结合的胞内小泡，并通过与第一个N末端卷曲区域(CC1)结合来抑制与细胞质动力蛋白的结合。与果蝇BicD CC3不同，BICD1CC3的晶体结构显示出不对称的平行同二聚螺旋结构和互补的节洞相互作用。此外，我们的结合研究表明，BICD1CC3与两种不同的货物Rab6和RanBP2都有结合面，并且CC1与Rab6的结合部位与Rab6的结合部位重叠。这些发现表明，在依赖动力蛋白的细胞内逆行运输过程中，BICD蛋白的货物识别和自身抑制具有分子基础。
Bicaudal-D1 (BICD1) is an α-helical coiled-coil protein mediating the attachment of specific cargo to cytoplasmic dynein. It plays an essential role in minus end-directed intracellular transport along microtubules. The third C-terminal coiled-coil region of BICD1 (BICD1 CC3) has an important role in cargo sorting, including intracellular vesicles associating with the small GTPase Rab6 and the nuclear pore complex Ran binding protein 2 (RanBP2), and inhibiting the association with cytoplasmic dynein by binding to the first N-terminal coiled-coil region (CC1). The crystal structure of BICD1 CC3 revealed a parallel homodimeric coiled-coil with asymmetry and complementary knobs-into-holes interactions, differing fromDrosophilaBicD CC3. Furthermore, our binding study indicated that BICD1 CC3 possesses a binding surface for two distinct cargos, Rab6 and RanBP2, and that the CC1-binding site overlaps with the Rab6-binding site. These findings suggest a molecular basis for cargo recognition and autoinhibition of BICD proteins during dynein-dependent intracellular retrograde transport.