通过protocadherin域相互作用进行神经元自我识别的分子逻辑
Rotem Rubinstein1, Chan Aye Thu2, Kerry Marie Goodman2
1Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA; Department of Systems Biology, Columbia University, New York, NY 10032, USA.
通过特定细胞的识别,集群的原素调解神经元的自我避开. 这项研究揭示了protocadherin域如何形成二元并相互作用以使神经发育过程中依赖大小的自我识别.
科学领域:
- 神经科学
- 分子生物学
- 结构生物学
背景情况:
- 在发育过程中,神经元自我避开对于正确的神经电路形成至关重要.
- 集群原素 (PCDHs) 通过随机,单个神经元的表达来调解自我回避.
- 通过PCDH介导的细胞识别的精确分子机制尚不完全理解.
研究的目的:
- 阐明聚类原卡德林异型特异性同性结合的结构基础.
- 了解PCDH细胞外素 (EC) 域如何调解细胞识别和自我避开.
- 为PCDH介导的自我识别提出一个分子模型.
主要方法:
- 从四种PCDH异型中确定EC1-EC3域结构的X射线晶体学.
- 生物物理测量 (例如表面等离子体共振).
- 细胞聚合试验和计算对接研究.
主要成果:
- 晶体结构显示了杆状的单体EC1-EC3域.
- 细胞之间的转结依赖于以反平行方向相互作用的EC1-EC4域.
- EC6域对于cis二次体的形成至关重要.
结论:
- 通过EC1-EC4域在对立的细胞表面上进行头到尾的相互作用.
- 这种相互作用形成了一个类似拉链的组合,介导了尺寸依赖的自我识别.
- 这些发现为了解神经元自我避开中的PCDH功能提供了结构框架.
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