维生素B-(12) -内在因子复合物的受体识别的结构基础
Christian Brix Folsted Andersen1, Mette Madsen, Tina Storm
1Department of Medical Biochemistry, Aarhus University, 8000 Aarhus C, Denmark.
Nature
|March 19, 2010
概括
维生素B12 (科巴胺) 的吸收依赖于内在因子和cubam受体. 这项研究揭示了IF-B12-cubilin复合物的晶体结构,解释了依赖的结合和维生素B12的吸收.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 分子医学是分子医学.
背景情况:
- 科巴胺 (维生素B12) 对哺乳动物至关重要,通过内在因子 (IF) 和cubam受体从饮食中吸收.
- 库巴姆受体包括库比林和无氨蛋白;缺陷导致维生素B12缺乏.
- 了解IF-B12-cubam相互作用对于解决缺乏症疾病至关重要.
研究的目的:
- 确定内在因子-可巴胺 (IF-Cbl) 和库比林CUB(5-8) 域之间的复合物的晶体结构.
- 阐明依赖的配体结合和维生素B12吸收的分子机制.
- 为了解可胺吸收的结构基础提供见解.
主要方法:
- 在3.3 Å分辨率的X射线晶体学.
- 确定IF-Cbl和cubilin CUB之间的复杂结构 ((5-8).
- 与LDL受体A型模块的结构比较.
主要成果:
- 确定了IF-Cbl和cubilin CUB ((5-8) 复合物的晶体结构.
- 多个CUB域在带结合中以模块化方式运行.
- 两个遥远的CUB域以依赖的方式结合IF,拥抱Cbl分子.
结论:
- 双点结合模型解释了Cbl如何间接诱导连接器-受体合.
- 涉及CUB域的依赖相互作用与LDL受体A型模块有相似之处.
- 基本联体残留物和酸性CUB域残留物之间的静电配对是Ca(2+) 依存相互作用的关键.
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