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通过冷电子显微镜揭示的可溶性α-klotho的形态景观

Nicholas J Schnicker^1,2, Zhen Xu¹, Mohammad Amir³

¹Protein and Crystallography Facility, University of Iowa Carver College of Medicine, Iowa City, Iowa, 52242, USA.

bioRxiv : the preprint server for biology

|March 18, 2024

概括

可溶性α-Klotho (sKLA) 存在于多种形式,揭示了其作为一种独立激素的潜力. 了解sKLA的理解

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:

α-Klotho (KLA) 是一种与FGFR一起作为FGF23的共受体的蛋白质.
可溶性KLA (sKLA) 的功能独立于FGFR/FGF23.
以前的结构表明sKLA仅作为FGF23.23的核心受体.

研究的目的:

为了研究apo-sKLA的生物物理性质和结构.
了解sKLA的FGFR/FGF23独立功能.
阐明sKLA.的形状景观.

主要方法:

质量光度测量用于评估溶液中的结构形成.
单颗粒冷电子显微镜 (cryo-EM) 用于结构确定.
3D可变性分析用于研究形状灵活性.

主要成果:

sKLA与FGFR,FGF23形成稳定的结构,并作为二聚体.
克里奥-EM显示了3.3Å分辨率结构的apo-sKLA.
与三元复合体相比,Apo-sKLA在其KL2域中表现出独特的特征和灵活性.
在apo-sKLA中的 conformational 变异性表明多个功能状态.

结论:

阿波-SKLA的形状可塑性支持其作为具有类作用的FGFR独立激素的作用.
了解sKLA的结构格局对于开发基于klotho的疗法至关重要.
这些发现扩大了sKLA已知的功能,超出了其作为FGF23共同受体的作用.

关键词:

三维可变性分析 (3DVA)纤维细胞生长因子 (FGF)可溶性α-克洛托 (sKLA) 是一种可溶性α-克洛托.低温电子显微镜 (cryo-EM) 的使用这就是Dimer Dimer的意思.一个单质的单质分子.三元复合体是一个三元复合体.

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