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Visualizing multistep elevator-like transitions of a nucleoside transporter

机译：可视化核苷转运蛋白的多步升降器样转变

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摘要

Membrane transporters move substrates across the membrane by alternating access of their binding sites between the opposite sides of the membrane. An emerging model of this process is the elevator mechanism, in which a substrate-binding transport domain moves a large distance across the membrane. This mechanism has been characterized by a transition between two states, but the conformational path that leads to the transition is not yet known, largely because the available structural information has been limited to the two end states. Here we present crystal structures of the inward-facing, intermediate, and outward-facing states of a concentrative nucleoside transporter from Neisseria wadsworthii. Notably, we determined the structures of multiple intermediate conformations, in which the transport domain is captured halfway through its elevator motion. Our structures present a trajectory of the conformational transition in the elevator model, revealing multiple intermediate steps and state-dependent conformational changes within the transport domain that are associated with the elevator-like motion.
机译：膜转运蛋白通过交替进入其在膜的相对侧之间的结合位点来使底物在膜上移动。该过程的新兴模型是升降机机制，其中底物结合转运域在膜上移动很大的距离。该机制的特征在于两个状态之间的转换，但是导致转换的构象路径尚不清楚，主要是因为可用的结构信息仅限于两个最终状态。在这里，我们介绍了奈瑟氏球菌（Neisseria wadsworthii）集中核苷转运蛋白的向内，中间和向外状态的晶体结构。值得注意的是，我们确定了多个中间构象的结构，其中运输域在其电梯运动的中途被捕获。我们的结构显示了电梯模型中构象转变的轨迹，揭示了与电梯运动类似的运输区域内的多个中间步骤和状态相关的构象变化。

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  • 来源
    《Nature》 |2017年第7652期|66-70|共5页
  • 作者

    Hirschi Marscha; Johnson Zachary Lee; Lee Seok-Yong;

  • 作者单位

    Duke Univ, Med Ctr, Dept Biochem, 303 Res Dr, Durham, NC 27710 USA;

    Duke Univ, Med Ctr, Dept Biochem, 303 Res Dr, Durham, NC 27710 USA;

    Duke Univ, Med Ctr, Dept Biochem, 303 Res Dr, Durham, NC 27710 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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