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脊椎动物非正规WNT5A信号发送中的ROR2囊丰富域的结构和功能
Samuel C Griffiths1, Jia Tan2, Armin Wagner3
1Division of Structural Biology, Wellcome Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
eLife
|May 23, 2024
概括
这就是ROR2受体.
科学领域:
- 分子生物学分子生物学
- 细胞信号传递 细胞信号传递
- 发展生物学 发展生物学
背景情况:
- ROR2是一种受体氨酸激酶,对非正规的WNT5A信号传输至关重要.
- WNT通路功能障碍导致发育障碍和转移性疾病.
- ROR2功能的特定领域和机制尚未完全理解.
研究的目的:
- 阐明ROR2域在WNT5A信号传输中的结构和功能作用.
- 通过ROR2.2研究WNT5A联体受体的机制.
- 探索ROR2与其他WNT受体的相互作用.
主要方法:
- 进行X射线晶体学以确定ROR2细胞外域的结构.
- 功能性测试以评估ROR2域在WNT5A信号传输中的作用.
- 基于抗体的实验来研究受体相互作用.
主要成果:
- 解决了ROR2的氨酸丰富域 (CRD) 和克林格尔 (Kr) 域的晶体结构.
- ROR2的CRD缺乏典型的脂质结合口袋,这表明一种新的联结体相互作用机制.
- 对于WNT5A信号传递,ROR2 CRD是必不可少且足够的,突变会影响分泌和功能.
- ROR2通过强化一个涉及Frizzled (FZ) 的受体复合体来转换WNT5A信号而起作用.
结论:
- ROR2利用其CRD进行WNT5A信号转导,与正规的脂质结合机制不同.
- ROR2的CRD对其分泌和功能至关重要,其破坏导致疾病表型.
- ROR2与复杂的Frizzled受体合作,调解WNT5A信号,突出了一个新的信号范式.
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