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ATP-binding cassette or ABC transporter is the largest superfamily of integral membrane proteins. The transporters have transmembrane-binding domains (TMDs) and nucleotide-binding domains (NBDs). The TMDs are specific to their substrates, whereas the NBDs are similar to engines that complete ATP hydrolysis to complete the substrate transport. They can be full transporters consisting of two TMDs and NBDs, half transporters with one TMD and NBD, while some encoded with a single TMD or NBD are...
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人类XPR1结构揭示了酸盐出口机制

Rui Yan1,2, Huiwen Chen1,3, Chuanyu Liu1,4

  • 1Laboratory of Soft Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing, China.

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研究人员发现了人类XPR1的结构,揭示了它是如何运输酸盐 (Pi) 的,并由内醇多酸盐 (InsPPs) 调节的. 这为了解细胞酸盐稳态提供了一个框架.

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科学领域:

  • 生物化学
  • 结构生物学
  • 细胞生物学

背景情况:

  • 无机酸盐 (Pi) 对于生命至关重要,
  • XPR1是人类唯一已知的Pi输出者, 对于细胞Pi平衡至关重要.
  • XPR1功能障碍与神经退行性疾病有关,这凸显了它的重要性.

研究的目的:

  • 阐明XPR1介导的Pi流动的结构机制.
  • 了解细胞内异醇多酸盐 (InsPPs) 对XPR1的调节.
  • 为 XPR1 门和 InsPP 传感提供结构基础.

主要方法:

  • 使用冷电子显微镜 (cryo-EM) 来确定人类XPR1的结构.
  • 获得了与Pi结合的封闭状态和开放状态以及与InsP6结合的形式.

主要成果:

  • 结构显示XPR1包括一个SPX域,一个核心域和一个Pi传输域.
  • 运输领域的三个基本集群是Pi绑定和运输的关键.
  • 一个保存的基 (W573) 作为一个关门开关,SPX域通过InsP6结合来调节Pi运输.

结论:

  • 这项研究提供了XPR1的高分辨率结构,详细介绍了其关和调节.
  • 这项工作提供了通过XPR1及其同类介导的Pi稳态的机制性理解.
  • 这些发现为未来研究XPR1功能和相关疾病奠定了基础.