电路布线中的氨酸功能的结构基础:突触中的毒素基因
Jingxian Li1, Moran Shalev-Benami2, Richard Sando3
1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA; Grossman Institute for Neuroscience, Quantitative Biology and Human Behavior, The University of Chicago, Chicago, IL 60637, USA.
Cell
|April 21, 2018
概括
色素 (TEN) 对于发育至关重要,与细菌毒素具有结构上的相似性. 在TEN2中的替代拼接调节细胞粘附和信号,影响神经发育.
科学领域:
- 结构生物学
- 神经科学
- 细胞粘附
背景情况:
- 阴尿素 (TEN) 是细胞表面粘附蛋白,对组织发育和轴突指导至关重要.
- 它们的精确结构机制和监管功能仍然不完全理解.
研究的目的:
- 阐明人类TEN2细胞外区域 (ECR) 的结构组织.
- 研究替代拼接在TEN2功能中的作用及其与latrophilin (LPHN) 的相互作用.
主要方法:
- 用冷电子显微镜 (cryo-EM) 确定人类TEN2 ECR的3.1-Å结构.
- 分析替代拼接变体及其对跨细胞粘附和信号的影响.
主要成果:
- TEN2 ECR具有独特的结构,具有β桶,类似免疫球蛋白的域和β螺旋,类似于细菌Tc毒素.
- 在β螺旋内,一个交替拼接的区域作为调节开关.
- 一种拼接变体促进了依赖于LPHN的跨细胞信号传递,而另一种则诱导了抑制后突触分化.
结论:
- 跨国网络的不同寻常的结构是它们在细胞过程中的不同作用的基础.
- 替代拼接TEN2提供了一个调节细胞粘附和神经发育的机制,与拉特罗菲林受体相互作用.
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