通过在其细胞外区域中的紧模块调节CELSR1的结构基础
Sumit J Bandekar1,2,3,4, Krassimira Garbett5, Szymon P Kordon1,2,3,4
1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA.
Nature communications
|April 28, 2025
概括
卡德林EGF拉米宁G七通G型受体亚家族 (CELSR/ADGRC) 对于发育至关重要. 这项研究揭示了CELSR1的紧结构.
科学领域:
- 结构生物学 结构生物学
- 分子生物学分子生物学
- 发展生物学 发展生物学
背景情况:
- 卡德林EGF拉米宁G七通G型受体亚家族 (CELSR/ADGRC) 是一种高度保存的粘附G蛋白结合受体家族,对动物发育至关重要.
- CELSR受体具有23个粘附域的大型细胞外区域 (ECR),但它们的分子功能仍然不太清楚.
- 了解CELSR功能的结构基础对于破译它们在发育过程中的作用至关重要.
研究的目的:
- 为了阐明小鼠CELSR1细胞外区域 (ECR) 的分子结构.
- 调查CELSR1领域的结构组织和功能影响.
- 提供关于CELSR介导的细胞-细胞粘附机制的见解.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 来确定小鼠CELSR1 ECR.的3.8 Å重建.
- 结构分析确定了在ECR内部形成紧模块的保守相互作用.
- 进行了基于细胞的测试,以评估特定的CELSR1域在细胞粘附中的功能作用.
主要成果:
- 在CELSR1 ECR中发现了一个包含14个域的紧模块,主要通过CADH9和C端GAIN域之间的相互作用进行介导.
- 在Ca2+的存在下,CELSR1 ECR形成了一个二元体,由反平行方向的卡德林重复介导.
- N端的CADH1-8重复对于细胞-细胞粘附至关重要,而C端的CADH9-GAIN模块则调节了粘附.
结论:
- 该研究揭示了CELSR1 ECR的结构组织,强调了功能模块的形成.
- 在CELSR1 ECR中的特定域在调解细胞-细胞粘附中发挥着独特的作用.
- 这项工作为大粘附G蛋白结合受体的功能提供了关键的分子洞察力.
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