肌酸酶VI的自抑制和激活通过其冷-EM结构揭示
Fengfeng Niu1,2, Lingxuan Li1, Lei Wang1
1Department of Neuroscience and Brain Research Center, School of Life Sciences, Southern University of Science and Technology, Shenzhen, Guangdong, China.
Nature communications
|February 8, 2024
概括
肌肉蛋白VI,一个独特的减分终端定向的电机,被揭示在一个自抑制状态. 它的紧结构阻断了活动,但像GIPC这样的货物适配器可以激活这种必不可少的分子电机.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 肌酸VI是一种独特的分子电机,朝着酸纤维的减数端移动.
- 它的活性对细胞功能至关重要,其失调与遗传疾病 (如聋和心肌病) 有关.
- 准确的调节肌肉蛋白VI活性的机制在很大程度上是未知的.
研究的目的:
- 阐明调节肌肉酶VI活性的分子机制.
- 为了确定自抑制肌肉蛋白VI的高分辨率结构.
- 了解货物结合如何影响肌肉蛋白VI的运动功能.
主要方法:
- 高分辨率冷电子显微镜 (cryo-EM) 用于确定肌VI的结构.
- 生物化学测定以评估ATPase活性和货物结合相互作用.
- 结构分析以确定关键的监管接口.
主要成果:
- 肌蛋白VI的自身抑制结构是紧的和单质的,头部和尾部域广泛相互作用.
- 一个长长的单α螺旋区域,称为"脊柱",调解这些抑制相互作用.
- 这种自身抑制的形状阻断了货物结合部位,并抑制了ATPase的活性.
- 货物适配器,如GIPC,破坏这些抑制相互作用,导致运动激活.
- 该结构为了解肌肉蛋白VI中与疾病相关的突变提供了基础.
结论:
- 肌酸VI是由通过分子内相互作用调节的自身抑制状态来调节的.
- 载荷结合适配器在激活肌酸VI运动功能的过程中起着至关重要的作用.
- 这些发现提供了对其他肌肉酶电机 (包括肌肉酶VII和X) 的调节的见解.
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