Cryo-EM Structure of Mechanosensitive Channel YnaI Using SMA2000: Challenges and Opportunities.

Cryo-EM Structure of Mechanosensitive Channel YnaI Using SMA2000: Challenges and Opportunities.
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DOI:
10.3390/membranes11110849
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发表时间:
2021-10-31
期刊:
影响因子:
4.2
通讯作者:
Guo Y
Guo Y
中科院分区:
工程技术4区
文献类型:
--
作者:
Catalano C;Ben-Hail D;Qiu W;Blount P;des Georges A;Guo Y

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机械敏感通道对施加在细胞膜上的机械力做出反应,并在调节细胞及其环境内的化学平衡中发挥重要作用。需要高分辨率结构信息来理解机械敏感通道的门控机制。蛋白质-脂质相互作用对于机械敏感通道的结构和功能完整性至关重要,但去垢剂无法维持纯化机械敏感通道的关键天然脂质环境。最近,无去污剂系统已成为膜蛋白结构生物学的替代品。该报告表明,虽然膜活性聚合物 SMA2000 可以在类机械敏感的 YnaI 通道的跨膜结构域上保留一些天然细胞膜脂质,但 YnaI 跨膜结构域的完整结构尚未解析。这揭示了 SMA2000 或类似膜活性共聚物的显着局限性。这种限制可能来自聚合物的异质性以及聚合物与 YnaI 跨膜结构域内相对较大的疏水口袋之间的非特异性相互作用。然而,这种限制为具有挑战性的膜蛋白的无去污剂技术提供了发展机会。
Mechanosensitive channels respond to mechanical forces exerted on the cell membrane and play vital roles in regulating the chemical equilibrium within cells and their environment. High-resolution structural information is required to understand the gating mechanisms of mechanosensitive channels. Protein-lipid interactions are essential for the structural and functional integrity of mechanosensitive channels, but detergents cannot maintain the crucial native lipid environment for purified mechanosensitive channels. Recently, detergent-free systems have emerged as alternatives for membrane protein structural biology. This report shows that while membrane-active polymer, SMA2000, could retain some native cell membrane lipids on the transmembrane domain of the mechanosensitive-like YnaI channel, the complete structure of the transmembrane domain of YnaI was not resolved. This reveals a significant limitation of SMA2000 or similar membrane-active copolymers. This limitation may come from the heterogeneity of the polymers and nonspecific interactions between the polymers and the relatively large hydrophobic pockets within the transmembrane domain of YnaI. However, this limitation offers development opportunities for detergent-free technology for challenging membrane proteins.
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