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Structural basis of mitochondrial receptor binding and constriction by DRP1

机译：DRP1结合和收缩线粒体受体的结构基础

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摘要

Mitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogues mitochondrial dynamics proteins of 49 and 51 kDa (MID49 and MID51) and mitochondrial fission factor (MFF); however, the mechanisms by which these proteins recruit and regulate DRP1 are unknown. Here we present a cryo-electron microscopy structure of full-length human DRP1 co-assembled with MID49 and an analysis of structure- and disease-based mutations. We report that GTP induces a marked elongation and rotation of the GTPase domain, bundle-signalling element and connecting hinge loops of DRP1. In this conformation, a network of multivalent interactions promotes the polymerization of a linear DRP1 filament with MID49 or MID51. After co-assembly, GTP hydrolysis and exchange lead to MID receptor dissociation, filament shortening and curling of DRP1 oligomers into constricted and closed rings. Together, these views of full-length, receptor- and nucleotide-bound conformations reveal how DRP1 performs mechanical work through nucleotide-driven allostery.
机译：线粒体遗传，基因组维持和代谢适应性取决于动力相关蛋白1（DRP1）及其线粒体受体的细胞器分裂。 DRP1受体包括49和51 kDa的旁系同源线粒体动力学蛋白（MID49和MID51）和线粒体裂变因子（MFF）。但是，这些蛋白募集和调节DRP1的机制尚不清楚。在这里，我们介绍了与MID49组装在一起的全长人DRP1的低温电子显微镜结构，并分析了基于结构和疾病的突变。我们报告说，GTP诱导明显延长和旋转的GTPase域，束信号元素和DRP1的连接铰链环。在这种构象中，多价相互作用的网络促进了线性DRP1细丝与MID49或MID51的聚合。共组装后，GTP的水解和交换导致MID受体解离，细丝缩短和DRP1低聚物卷曲成狭窄和闭合的环。这些关于全长，受体和核苷酸结合构象的观点共同揭示了DRP1如何通过核苷酸驱动的构象物执行机械作用。

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  • 来源
    《Nature》 |2018年第7710期|401-405|共5页
  • 作者

    Kalia Raghav; Wang Ray Yu-Ruei; Yusuf Ali; Thomas Paul V.; Agard David A.; Shaw Janet M.; Frost Adam;

  • 作者单位

    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA;

    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA;

    Univ Utah, Dept Biochem, Salt Lake City, UT 84112 USA;

    Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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  • 正文语种 eng
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