核心平面细胞极性蛋白CELSR1具有弱粘性和灵活性的阴素ectodomain
Elakkiya Tamilselvan1, Marcos Sotomayor1
1Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH 43210, USA; Biophysics Program, The Ohio State University, Columbus, OH 43210, USA.
Structure (London, England : 1993)
|February 2, 2024
概括
平面细胞极性蛋白CELSR1 是一个平面细胞极性蛋白.
科学领域:
- 细胞生物学 细胞生物学
- 发展生物学 发展生物学
- 结构生物学 结构生物学
背景情况:
- 平面细胞极性 (PCP) 对于组织发育至关重要,并依赖于细胞极化和对齐.
- CELSR1,一种非典型的素,是PCP的核心,具有复杂的ectodomain与素重复和粘附GPCR域.
- 之前的研究表明CELSR1具有同性附着性,但潜在的机制尚不清楚.
研究的目的:
- 为了研究CELSR1细胞外阴素 (EC) 的粘合性和结构特征,CELSR1的细胞外阴素 (EC) 重复.
- 为了阐明CELSR1-介导的细胞粘附的机制细节.
- 为了确定在平面细胞极性中控制CELSR1功能的结构决定因素.
主要方法:
- 使用珠子聚合测试来评估CELSR1 EC重复的粘合能力.
- 针对特定的CELSR1 EC域进行了基于溶液的二元化实验.
- 确定了人类CELSR1 EC1-4和EC4-7片段的晶体结构.
- 使用计算模拟来分析EC4-7.7的灵活性.
主要成果:
- 珠子聚合试验没有支持仅通过CELSR1 EC重复介导的强粘附.
- 只有在溶液中的高度下,CELSR1 EC1-4才显示出二分化.
- 晶体结构显示了EC1-4和EC4-7的正规折叠,EC5和EC6.7之间有一个非正规的链接器.
- 实验和模拟表明EC5-6链接器的灵活性,以及EC7-MAD10介导的二分化.
结论:
- CELSR1 阴素重复表现出较弱的同类粘附性.
- 结构灵活性,特别是EC5-6链接器和EC7-MAD10域,有助于CELSR1-介导的二分化和功能.
- 这些发现为CELSR1在平面细胞极性中的作用的结构基础提供了机械的见解.
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