Myomaker的冷-EM结构揭示了肌肉细胞融合的分子基础
Tao Long1, Yichi Zhang2, Linda Donnelly1
1Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nature structural & molecular biology
|September 28, 2023
概括
研究人员发现了Myomaker的结构,Myomaker是一种对骨肌肉形成至关重要的蛋白质. 这一发现揭示了Myomaker如何促进细胞融合,为肌肉发育和修复提供了洞察力.
科学领域:
- 生物化学 生化学
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
背景情况:
- 骨肌的形成依赖于单核肌细胞的融合成多核肌纤维.
- 肌细胞制造者是关键的骨肌肉特异性膜蛋白,对于这种肌细胞融合过程是必不可少的.
研究的目的:
- 为了确定鼠标Myomaker (mMymk) 和Ciona robusta Myomaker (cMymk) 的冷电子显微镜 (cryo-EM) 结构.
- 阐明Myomaker在调解细胞融合中的结构基础和功能意义.
主要方法:
- 电子显微镜 (cryo-EM) 用于解析mMymk和cMymk的结构.
- 功能性分析,包括异质细胞-细胞融合试验,以评估结构特征在融合活性中的作用.
主要成果:
- 肌造物体表现出一种与G蛋白结合的受体类折叠,具有七个跨膜螺旋 (TMs).
- TMs 2-4 形成一个二维接口,而 TMs 3 和 5-7 构成一个对功能至关重要的脂质结合部位.
- mMymk和cMymk之间的结构相似性表明,物种之间存在着保存的融合机制.
- 功能性测试证实了二次接口和脂质结合部位对于Myomaker的融合活性是必要的.
结论:
- 该研究提供了Myomaker的高分辨率冷EM结构,揭示了其独特的折叠和功能域.
- 结构和功能洞察力强调了二维接口和脂质相互作用对于Myomaker介导的肌细胞融合的重要性.
- 研究结果表明,在进化上遥远的物种中,由Myomaker调解的细胞融合的保存机制存在,这对了解肌肉发育和疾病有意义.
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