Graduate School of Advanced Science and Engineering, Hiroshima University, Hiroshima 739-8511, Japan.
Graduate School of Engineering, Tottori University, Tottori 680-8552, Japan.
Langmuir. 2024 Oct 1;40(39):20537-20549. doi: 10.1021/acs.langmuir.4c02178. Epub 2024 Sep 16.
α-Synuclein (αS) causes Parkinson's disease due to the structural alteration into amyloid fibrils that form after the interaction with synaptic membranes in neurons. To understand the alternation mechanism, the effect of salt (NaCl) on the interaction of αS with synaptic mimic membrane was characterized at the molecular level because salt triggered the amyloid fibril formation. The membrane-bound conformation (or the initial conformation before fibrillation) showed that NaCl decreased the number of helical structures and Tyr residues interacting with the membrane surface compared to when NaCl was absent, implying an increase in solvent-exposed regions. The N-terminal region of αS interacted with the membrane, forming the helical structures regardless of NaCl, while the C-terminal region formed a random structure with weak membrane interaction, but NaCl inhibited the interaction of its hydrophobic area, suggesting that salt promoted amyloid fibril formations by exposing the hydrophobic C-terminal region, which can intermolecularly interact with free αS.
α-突触核蛋白（αS）通过与神经元突触膜相互作用后结构改变为淀粉样纤维，导致帕金森病。为了了解这种改变的机制，我们在分子水平上研究了盐（NaCl）对 αS 与突触模拟膜相互作用的影响，因为盐会触发淀粉样纤维的形成。膜结合构象（或纤维形成前的初始构象）表明，与没有 NaCl 时相比，NaCl 减少了与膜表面相互作用的螺旋结构和 Tyr 残基的数量，这意味着溶剂暴露区域增加。αS 的 N 端区域与膜相互作用，形成螺旋结构，而不管是否有 NaCl，而 C 端区域形成与膜弱相互作用的无规结构，但 NaCl 抑制了其疏水区的相互作用，这表明盐通过暴露疏水性 C 端区域来促进淀粉样纤维的形成，该区域可以与游离的 αS 分子间相互作用。
