Département de Biochimie, Microbiologie et Bio-informatique, Institut de Biologie Intégrative et des Systèmes, and Centre de Recherche sur la Fonction, la Structure et l'Ingénierie des Protéines, Université Laval, Quebec City, Quebec, Canada.
Biophys J. 2012 May 16;102(10):2270-8. doi: 10.1016/j.bpj.2012.04.003. Epub 2012 May 15.
Knowledge about the influenza fusion peptide (FP) membrane insertion mode is crucial for understanding its fusogenic mechanism. NMR and electron paramagnetic resonance experiments showed that in micelles, the FP inserted as a fixed-angle inverted V. In membranes, however, it was shown to insert as a straight α-helix (by molecular-dynamics simulations) and to adopt multiple kinked conformations (by solid-state NMR). In this work we performed explicit-solvent molecular-dynamics simulations of the influenza FP, and its F9A and W14A mutants, in POPC membranes. The Hα1 chemical shifts predicted from the molecular-dynamics structures are in excellent agreement with the experimental values obtained for the three peptides. The peptide orientation and conformations observed from the simulations lead to a flexible flat-V model in which the peptide lies almost flat on the membrane surface and alternates between kinked and straight-helix conformations.
关于流感融合肽（FP）的膜插入模式的知识对于理解其融合机制至关重要。NMR 和电子顺磁共振实验表明，在胶束中，FP 以固定角度的反向 V 形插入。然而，在膜中，它被证明以直的α-螺旋形式插入（通过分子动力学模拟）并采用多种扭曲构象（通过固态 NMR）。在这项工作中，我们在 POPC 膜中对流感 FP 及其 F9A 和 W14A 突变体进行了显式溶剂分子动力学模拟。从分子动力学结构预测的 Hα1 化学位移与为三种肽获得的实验值非常吻合。从模拟中观察到的肽取向和构象导致了一种灵活的平 V 模型，其中肽几乎平放在膜表面上，并在扭曲和直螺旋构象之间交替。
