Molecular Sensing and Manipulation of Protein Oligomerization in Membrane Nanotubes with Bolaamphiphilic Foldamers.
Molecular Sensing and Manipulation of Protein Oligomerization in Membrane Nanotubes with Bolaamphiphilic Foldamers.
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膜纳米管中蛋白质齐聚的分子传感和操纵。
DOI：
10.1021/jacs.3c05753
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发表时间：
2023-11-22
影响因子：
15
通讯作者：
Frolov, Vadim A.
中科院分区：
文献类型：
--
作者：
Aftahy, Kathrin;Arrasate, Pedro;Bashkirov, Pavel V.;Kuzmin, Petr I.;Maurizot, Victor;Huc, Ivan;Frolov, Vadim A.
蛋白质超分子结构的自适应和可逆自组装是动态生命物质的基本特征。然而，从小的和动态的寡聚体前体中出现的中尺度蛋白质复合物的定量检测和评估仍然具有很大的挑战性。在这里，我们提出了一种新的方法，利用短膜纳米管（sNT）拉从平面膜水库作为nanotemplate分子重建，操纵和传感蛋白质寡聚化和自组装在介观尺度。sNT报告了由膜结合蛋白引起的膜形状和刚度的变化，作为sNT腔的离子电导率的变化。为了将低聚限制在sNT上，我们设计并合成了刚性低聚酰胺折叠带（ROFT）。带电荷的ROFT并入平面膜和sNT膜中，介导蛋白质与膜的结合，并且在腔电场的驱动下，使结合的蛋白质在sNT和平面膜之间穿梭。使用膜联蛋白-V（AnV）作为原型，我们表明，sNT检测到AnV低聚物穿梭到纳米管的ROFT。AnV在sNT上的积累诱导其自组装成弯曲的晶格，限制sNT的几何形状并抑制在sNT延伸期间从储库中摄取材料，导致sNT裂变。通过比较自发的和ROFT介导的进入sNT的AnV，我们揭示了如何复杂的膜曲率传感小AnV寡聚体控制的晶格自组装。这些结果建立sNT-ROFT作为一个强大的工具，分子重建和功能分析的蛋白质寡聚化和自组装，广泛应用于各种膜过程。
Adaptive and reversible self-assembly of supramolecular protein structures is a fundamental characteristic of dynamic living matter. However, the quantitative detection and assessment of the emergence of mesoscale protein complexes from small and dynamic oligomeric precursors remains highly challenging. Here, we present a novel approach utilizing a short membrane nanotube (sNT) pulled from a planar membrane reservoir as nanotemplates for molecular reconstruction, manipulation, and sensing of protein oligomerization and self-assembly at the mesoscale. The sNT reports changes in membrane shape and rigidity caused by membrane-bound proteins as variations of the ionic conductivity of the sNT lumen. To confine oligomerization to the sNT, we have designed and synthesized rigid oligoamide foldamer tapes (ROFTs). Charged ROFTs incorporate into the planar and sNT membranes, mediate protein binding to the membranes, and, driven by the luminal electric field, shuttle the bound proteins between the sNT and planar membranes. Using Annexin-V (AnV) as a prototype, we show that the sNT detects AnV oligomers shuttled into the nanotube by ROFTs. Accumulation of AnV on the sNT induces its self-assembly into a curved lattice, restricting the sNT geometry and inhibiting the material uptake from the reservoir during the sNT extension, leading to the sNT fission. By comparing the spontaneous and ROFT-mediated entry of AnV into the sNT, we reveal how intricate membrane curvature sensing by small AnV oligomers controls the lattice self-assembly. These results establish sNT-ROFT as a powerful tool for molecular reconstruction and functional analyses of protein oligomerization and self-assembly, with broad application to various membrane processes.
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