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首页> 外文期刊>Crystal growth & design >Lipidic Cubic Phase-Induced Membrane Protein Crystallization: Interplay Between Lipid Molecular Structure, Mesophase Structure and Properties, and Crystallogenesis
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Lipidic Cubic Phase-Induced Membrane Protein Crystallization: Interplay Between Lipid Molecular Structure, Mesophase Structure and Properties, and Crystallogenesis

机译:脂质立方相诱导的膜蛋白结晶:脂质分子结构,中间相结构和性能之间的相互作用,以及结晶性

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摘要

Obtaining well-diffracting crystals of membrane proteins, which is crucial to the molecular-level understanding of their intrinsic three-dimensional structure, dynamics, and function, represents a fundamental bottleneck in the field of structural biology. One of the major advances in the field of membrane protein structural determination was the realization that the nanostructured lipidic cubic phase (LCP) environment constitutes a membrane mimetic matrix that promotes solubilization, stabilization, and crystallization of specific membrane proteins. Despite two decades passing since the introduction of LCP-based membrane protein crystallization, the research community's understanding of the processes that drive protein nucleation and macromolecular assembly in the LCP generally remains limited. In the current study, we present a detailed, systematic investigation into the relationship between the chemical structure of the lipid, the physical properties of the ensuing mesophase, the translational diffusion of the encapsulated membrane protein, and the resulting protein crystallization. Importantly, we show for the first time that cubic phase transport properties directly modulate the size and morphology of fully grown protein crystals without affecting their crystallographic space group. These findings provide a deeper understanding of the LCP-based crystal growth process, setting the stage for the engineering of membrane protein crystals at the molecular level via intentional design of the host cubic phase, and, ultimately, accelerating progress in the field of membrane protein structural biology.
机译:获得对膜蛋白的良好衍生晶体,这对其内在三维结构,动力学和功能的分子水平理解至关重要,代表了结构生物学领域的基本瓶颈。膜蛋白结构测定领域的主要进步之一是认识到纳米结构脂质立方相(LCP)环境构成膜模拟基质,其促进特异性膜蛋白的溶解,稳定和结晶。尽管经过二十年来以来引进基于LCP的膜蛋白结晶以来,研究界对驱动蛋白质成核和高分子组件在LCP中的过程的理解通常仍然有限。在目前的研究中,我们向脂质的化学结构之间的关系,随后的中间相的物理性质,包封膜蛋白的平移扩散,以及所得蛋白质结晶的脂质结构的详细,系统化。重要的是,我们首次展示了立方相传性质的第一次直接调节完全生长的蛋白质晶体的大小和形态而不影响其晶体间隙基团。这些发现提供了对基于LCP的晶体生长过程的更深入了解,通过有意设计宿主立方相的分子水平设定膜蛋白质晶体的工程阶段,最终在膜蛋白蛋白领域进展结构生物学。

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  • 来源
    《Crystal growth & design》 |2017年第11期|共8页
  • 作者单位

    RMIT Univ Coll Sci Engn &

    Hlth Sch Sci 124 La Trobe St Melbourne Vic 3000 Australia;

    Univ Melbourne Sch Chem Melbourne Vic 3010 Australia;

    Univ Melbourne Dept Med Biol Melbourne Vic 3010 Australia;

    Univ Melbourne Inst Bio21 Melbourne Vic 3010 Australia;

    CSIRO Biomed Mfg Program 343 Royal Parade Parkville Vic 3052 Australia;

    CSIRO Biomed Mfg Program 343 Royal Parade Parkville Vic 3052 Australia;

    Univ Melbourne Sch Chem Melbourne Vic 3010 Australia;

    RMIT Univ Coll Sci Engn &

    Hlth Sch Sci 124 La Trobe St Melbourne Vic 3000 Australia;

    Univ Melbourne Dept Med Biol Melbourne Vic 3010 Australia;

    Univ Melbourne Dept Med Biol Melbourne Vic 3010 Australia;

    Univ Zurich Dept Chem CH-8057 Zurich Switzerland;

    RMIT Univ Coll Sci Engn &

    Hlth Sch Sci 124 La Trobe St Melbourne Vic 3000 Australia;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 晶体学;
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