粘附GPCR CELSR1的细胞外区域结构显示了一个紧的模块,该模块调节了G蛋白合
bioRxiv : the preprint server for biology
|February 8, 2024
概括
卡德林受体 (CELSR) 对动物发育至关重要. 这项研究揭示了CELSR1的结构.
科学领域:
- 细胞生物学 细胞生物学
- 结构生物学 结构生物学
- 生物化学 生物化学
背景情况:
- 卡德林EGF拉米宁G七通道G型受体 (CELSRs) 是关键的粘附G蛋白合受体,对动物发育至关重要.
- CELSRs具有复杂的细胞外区域 (ECR),具有23个粘附域,将细胞粘附与细胞内信号通路联系起来.
- 关于CELSR功能的精确机制,在分子层面上只有有限的理解.
研究的目的:
- 确定小鼠CELSR1细胞外区域 (mCELSR1 ECR) 的分子结构.
- 阐明特定的CELSR1域在细胞粘附和G蛋白信号传递中的作用.
- 为保存的CELSR受体家族提供结构性见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来重建mCELSR1 ECR,分辨率为4.3 Å.
- 生物化学测试被用来评估细胞粘附性质.
- 用G蛋白合试验来研究信号调节.
主要成果:
- mCELSR1 ECR的冷EM结构解析了13个域,揭示了由域间相互作用形成的紧模块.
- 在Ca2+的存在下,mCELSR1 ECR采用了扩展形状,被认为是一种反平行阴素重复二次体.
- 确定N端的CADH1-8模块对于细胞粘附至关重要,而C端的CAHD9-GAIN模块则调节信号传输.
结论:
- 这项研究为CELSR1 ECR的结构和功能提供了前所未有的分子洞察力.
- 这些发现阐明了N端和C端域在调解细胞粘附和信号传导方面的不同作用.
- 这项工作为未来对CELSR和相关的粘附G蛋白结合受体的机制研究奠定了基础.
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