在SLC38A9中的pH依赖调节
Xuelang Mu1,2, Ampon Sae Her1, Tamir Gonen1,2,3
1Departments of Biological Chemistry and Physiology, University of California, Los Angeles, CA, USA.
bioRxiv : the preprint server for biology
|November 24, 2025
概括
lysosomal 运输体 SLC38A9 是一个
科学领域:
- 细胞生物学 细胞生物学
- 生物化学 生物化学
- 分子机制的分子机制
背景情况:
- 细胞需要严格的代谢调节来适应环境.
- 拉巴胺素复合体1 (mTORC1) 途径的机械标调节细胞生长和新陈代谢,感知营养的可用性,特别是氨基酸.
- 溶解体对于营养回收和维护氨基酸平衡至关重要.
研究的目的:
- 为了研究 lysosomal 氨基酸载体 SLC38A9.9 的pH 相关调节.
- 确定涉及pH感应的特定残留物及其作用机制.
- 阐明SLC38A9.9的pH诱导激活的结构基础.
主要方法:
- 生物化学试验测量SLC38A9.9.通过SLC38A9.9.通过SLC38A9.9.通过SLC38A9.通过SLC38A9.
- 在His544.4的histidine残留物的位点定向突变发生.
- 在不同的pH值下确定SLC38A9晶体结构.
- 进行比较结构分析以模拟pH诱导的形状变化.
主要成果:
- 通过SLC38A9进行的氨酸运输受到pH的显著影响.
- 鉴定出了histidine残留物His544作为关键的pH传感器,它调解了pH依赖的传输.
- 突变His544取消了pH敏感性,但没有影响基底运输活动.
- 结构比较揭示了SLC38A9在高和低pH的不同构造,支持pH诱导激活模型.
结论:
- SLC38A9的活性受 lysosomal pH 的调节.
- 希斯544在感知pH值变化和调节传送器功能方面发挥着关键作用.
- 这些发现揭示了 lysosomal 载体调节的新机制及其对mTORC1信号传递的影响.
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