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合成聚合物形成所需的納米盤的方法介紹

瀏覽次數(shù):1158 發(fā)布日期:2023-5-4  來源:本站 僅供參考,謝絕轉載,否則責任自負
合成納米盤是小尺寸的盤狀結構體,由細胞膜磷脂組成,而磷脂則通過合成聚合物環(huán)結合在一起。
 
圖 1:合成納米盤描述
 
    納米盤提供了細胞膜中天然膜蛋白環(huán)境的可遷移、幾乎一致的復制品。因此,它們規(guī)避了增溶去污劑的問題,使我們能夠在活性狀態(tài)下保持膜蛋白穩(wěn)定或對其進行分離,以便開展進一步的科學研究。
 
有幾種不同的聚合物可用于制造合成納米盤,各有其優(yōu)缺點。
 
 
 
合成聚合物如何形成所需的納米盤?
 
 
細胞膜為最重要的蛋白質組之一提供了其所需的環(huán)境:膜蛋白質組。膜蛋白分為外周蛋白和整合蛋白兩種,二者均具有一定的疏水性,在正常條件下不易溶解。
 
問題是,當這些疏水區(qū)與水或其他親水性介質接觸時,膜蛋白的 3D 結構將坍塌,從而失去其功能性。

為避免這種情況發(fā)生,蛋白質研究科學家通常使用去污劑(洗滌劑)來覆蓋膜蛋白的這些脆弱部分。但由于使用去污劑的方法也有其自身的一系列問題,如篩選過程耗時長或3D 結構的干擾等情況。

相比之下,合成聚合物能夠從其單體中形成聚合物鏈,插入所需的目標膜蛋白周圍的細胞膜之中(見圖2,頂部紅線)。像餅干模具(cookie cutter)一樣,將膜蛋白從膜中溶解出來,而聚合物則使膜蛋白在新形成的納米盤中保持穩(wěn)定。
 
接下來采用親和層析法精確分離穩(wěn)定的目標蛋白,并實施進一步的科學分析。
 
 
圖2:在包含膜蛋白的天然細胞膜中制備合成納米盤的過程。下一個步驟一般為親和層析。
 

已發(fā)表文獻:

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8. Brown et al.Structural biology of endogenous membrane protein assemblies in native nanodiscs.Virginia Tech, USA.
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11. Overduin et al.Structures and Dynamics of Native-State Transmembrane Protein Targets and Bound Lipids.University of Alberta, USA.
12. Zhou et al.Conformations of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoproteins 2  in Detergents and Styrene-Maleic Acid Lipid Particles (SMALPs).Dana-Farber Cancer Institute, USA.
13. Marconnet et al.Influence of Hydrophobic Groups Attached to Amphipathic Polymers on the Solubilization of Membrane Proteins along with Their Lipids.University of Paris, FR.
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15. Zhou et al.Conformations of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoproteins 2  in Detergents and Styrene-Maleic Acid Lipid Particles (SMALPs).Dana-Farber Cancer Institute, USA.
16. Zhou et al.Conformations of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoproteins 2  in Detergents and Styrene-Maleic Acid Lipid Particles (SMALPs).Dana-Farber Cancer Institute, USA.
17. Hernandez & Levental.Lipid packing is disrupted in copolymeric nanodiscs compared to intact membranes.University of Virginia, USA.
18. Zhou et al.Conformations of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoproteins 2  in Detergents and Styrene-Maleic Acid Lipid Particles (SMALPs).Dana-Farber Cancer Institute, USA.
19. Zhou et al.Conformations of the Human Immunodeficiency Virus (HIV-1) Envelope Glycoproteins 2  in Detergents and Styrene-Maleic Acid Lipid Particles (SMALPs). Dana-Farber Cancer Institute, USA.

 
 
 
 
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