Department of Chemistry and Biochemistry, The University of Texas at Dallas, Richardson, TX, USA.
Institute of Physical and Theoretical Chemistry, Graz University of Technology, Graz, Austria.
Nat Commun. 2021 Apr 13;12(1):2202. doi: 10.1038/s41467-021-22285-y.
Artificial native-like lipid bilayer systems constructed from phospholipids assembling into unilamellar liposomes allow the reconstitution of detergent-solubilized transmembrane proteins into supramolecular lipid-protein assemblies called proteoliposomes, which mimic cellular membranes. Stabilization of these complexes remains challenging because of their chemical composition, the hydrophobicity and structural instability of membrane proteins, and the lability of interactions between protein, detergent, and lipids within micelles and lipid bilayers. In this work we demonstrate that metastable lipid, protein-detergent, and protein-lipid supramolecular complexes can be successfully generated and immobilized within zeolitic-imidazole framework (ZIF) to enhance their stability against chemical and physical stressors. Upon immobilization in ZIF bio-composites, blank liposomes, and model transmembrane metal transporters in detergent micelles or embedded in proteoliposomes resist elevated temperatures, exposure to chemical denaturants, aging, and mechanical stresses. Extensive morphological and functional characterization of the assemblies upon exfoliation reveal that all these complexes encapsulated within the framework maintain their native morphology, structure, and activity, which is otherwise lost rapidly without immobilization.
人工类天然脂质双层系统由磷脂组装成单层脂质体构成，允许去污剂溶解的跨膜蛋白重构成称为脂蛋白体的超分子脂质 - 蛋白组装体，模拟细胞膜。由于这些复合物的化学组成、膜蛋白的疏水性和结构不稳定性以及胶束和脂质双层中蛋白、去污剂和脂质之间相互作用的不稳定性，它们的稳定化仍然具有挑战性。在这项工作中，我们证明可以成功地生成和固定亚稳脂质、蛋白-去污剂和蛋白-脂质超分子复合物在沸石咪唑骨架 (ZIF) 中，以增强它们对化学和物理胁迫的稳定性。在 ZIF 生物复合材料、空白脂质体以及去污剂胶束中的模型跨膜金属转运体或嵌入脂蛋白体中的固定化后，抵抗高温、化学变性剂暴露、老化和机械应力。对复合材料进行广泛的形态和功能表征，揭示了封装在该框架中的所有这些复合物都保持其天然形态、结构和活性，否则在没有固定化的情况下会迅速丢失。
