Laboratory of Neurobiology, Max-Planck-Institute for Biophysical Chemistry, Göttingen, Germany.
Department of Molecular Pharmacology & Cell Biology, Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.
Nat Commun. 2021 Jun 14;12(1):3606. doi: 10.1038/s41467-021-23722-8.
Membrane fusion is fundamental to biological processes as diverse as membrane trafficking or viral infection. Proteins catalyzing membrane fusion need to overcome energy barriers to induce intermediate steps in which the integrity of bilayers is lost. Here, we investigate the structural features of tightly docked intermediates preceding hemifusion. Using lipid vesicles in which progression to hemifusion is arrested, we show that the metastable intermediate does not require but is enhanced by divalent cations and is characterized by the absence of proteins and local membrane thickening. Molecular dynamics simulations reveal that thickening is due to profound lipid rearrangements induced by dehydration of the membrane surface.
膜融合是多种生物过程的基础，如膜运输或病毒感染。催化膜融合的蛋白质需要克服能量障碍，诱导双层膜完整性丧失的中间步骤。在这里，我们研究了在半融合之前紧密对接的中间产物的结构特征。使用进展到半融合被阻止的脂质囊泡，我们表明，亚稳定中间产物不需要但被二价阳离子增强，并且其特征为缺乏蛋白质和局部膜增厚。分子动力学模拟表明，增厚是由于膜表面脱水引起的深刻脂质重排。
