Makasewicz Katarzyna, Wennmalm Stefan, Linse Sara, Sparr Emma
Department of Physical Chemistry, Lund University, 221 00 Lund, Sweden.
Department of Applied Physics, SciLifeLab, Royal Institute of Technology, 171 65 Solna, Sweden.
QRB Discov. 2022 Jul 25;3:e10. doi: 10.1017/qrd.2022.9. eCollection 2022.
-Synuclein is a small neuronal protein that reversibly associates with lipid membranes. The membrane interactions are believed to be central to the healthy function of this protein involved in synaptic plasticity and neurotransmitter release. -Synuclein has been speculated to induce vesicle fusion as well as fission, processes which are analogous to each other but proceed in different directions and involve different driving forces. In the current work, we analyse -synuclein-induced small unilamellar vesicle deformation from a thermodynamics point of view. We show that the structures interpreted in the literature as fusion intermediates are in fact a stable deformed state and neither fusion nor vesicle clustering occurs. We speculate on the driving force for the observed deformation and put forward a hypothesis that -synuclein self-assembly on the lipid membrane precedes and induces membrane remodelling.
α-突触核蛋白是一种与脂质膜可逆结合的小神经元蛋白。膜相互作用被认为对于该蛋白参与突触可塑性和神经递质释放的健康功能至关重要。有人推测α-突触核蛋白可诱导囊泡融合以及裂变，这两个过程彼此类似，但方向相反且涉及不同的驱动力。在当前工作中，我们从热力学角度分析了α-突触核蛋白诱导的小单层囊泡变形。我们表明，文献中解释为融合中间体的结构实际上是一种稳定的变形状态，既不会发生融合也不会发生囊泡聚集。我们推测了观察到的变形的驱动力，并提出了一个假设，即α-突触核蛋白在脂质膜上的自组装先于并诱导膜重塑。
