The assembly of protein actin into double-helical filaments promotes many eukaryotic cellular processes that are regulated by actin-binding proteins (ABPs). Actin filaments can adopt multiple conformations, known as structural polymorphism, which possibly influences the interaction between filaments and ABPs. Gelsolin is a Ca2+ -regulated ABP that severs and caps actin filaments. Gelsolin binding modulates filament structure; however, it is not known how polymorphic actin filament structures influence an interaction of gelsolin S1 with the barbed-end of filament. Herein, we investigated how polymorphic structures of actin filaments affect the interactions near interfaces between the gelsolin segment 1 (S1) domain and the filament barbed-end. Using all-atom molecular dynamics simulations, we demonstrate that different tilted states of subunits modulate gelsolin S1 interactions with the barbed-end of polymorphic filaments. Hydrogen bonding and interaction energy at the filament-gelsolin S1 interface indicate distinct conformations of filament barbed ends, resulting in different interactions of gelsolin S1. This study demonstrates that filament's structural multiplicity plays important roles in the interactions of actin with ABPs.

中文翻译：

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多态肌动蛋白丝与凝溶胶蛋白segment-1之间相互作用的分子动力学研究。

蛋白质肌动蛋白组装成双螺旋细丝会促进许多由肌动蛋白结合蛋白（ABP）调控的真核细胞过程。肌动蛋白丝可以采取多种构象，称为结构多态性，这可能会影响丝与ABP之间的相互作用。凝溶胶蛋白是一种Ca2 +调节的ABP，可切断并封闭肌动蛋白丝。凝溶胶蛋白的结合调节细丝结构；然而，尚不清楚多态肌动蛋白丝结构如何影响凝溶胶蛋白S1与丝的带刺末端的相互作用。在这里，我们研究了肌动蛋白丝的多态结构如何影响凝溶胶蛋白节段1（S1）域和丝的有刺末端之间的界面附近的相互作用。使用全原子分子动力学模拟，我们证明了不同倾斜状态的亚基调节凝溶胶蛋白S1与多态长丝的倒刺端的相互作用。细丝-凝溶胶蛋白S1界面处的氢键和相互作用能表明细丝带刺末端的构象不同，从而导致凝溶胶蛋白S1发生不同的相互作用。这项研究表明，细丝的结构多样性在肌动蛋白与ABP的相互作用中起着重要作用。