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发送使用Na+流动以释放脂质修饰的

Qianqian Wang¹, Daniel E Asarnow², Ke Ding¹

¹Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, CA, USA.

|October 28, 2021

概括

发送的蛋白质 (DISP1) 通过跨膜通道促进子蛋白质的输出. 这一过程由 (Na+) 流提供动力,这对胚胎发育至关重要,并且在相关的传送器中保存.

科学领域:

生物化学
分子生物学
结构生物学

背景情况:

发送蛋白 (DISP1) 对于从胚胎表达部位释放脂质修饰的刺蛋白至关重要,使组织模式成为可能.
DISP1属于一个包含NPC1,PTCH1和RND家族成员的传输器家族,这表明传输机制是保存的.

研究的目的:

确定鼠标DISP1的冷电子显微镜结构.
阐明 DISP1 促进刺蛋白质出口的机制,重点关注离子运输的作用.

主要方法:

用冷电子显微镜测定小鼠DISP1的结构.
生物化学测试以评估突变对DISP1功能和出口的影响.
在DISP1跨膜通道内的离子协调分析.

主要成果:

冷-EM结构显示了DISP1中的一个跨膜通道,协调了三种Na+离子.
刺出口率取决于通过等离子体膜的Na+梯度.
破坏Na+协调的突变 (DISP1-NNN) 损害了Hedgehog的出口,同时保持了结合性.
ShhN 与 DISP1 的结合取决于形状,并与 Na+ 位点占用有关.

结论:

通过DISP1从膜中提取脂质链接的子信号.
在DISP1中的Na+协调残留物保留在PTCH1和RND家族成员中,这表明离子驱动的传输机制保留了.
DISP1的机制涉及由Na+结合和流量调节的形状变化,这对发育信号至关重要.

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