Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Department of Chemistry and Biochemistry, University of California, Los Angeles, Los Angeles, CA 90095, USA.
Angew Chem Int Ed Engl. 2022 Jun 20;61(25):e202108501. doi: 10.1002/anie.202108501. Epub 2022 Apr 21.
Antimicrobial peptides (AMPs) preferentially permeate prokaryotic membranes via electrostatic binding and membrane remodeling. Such action is drastically suppressed by high salt due to increased electrostatic screening, thus it is puzzling how marine AMPs can possibly work. We examine as a model system, piscidin-1, a histidine-rich marine AMP, and show that ion-histidine interactions play unanticipated roles in membrane remodeling at high salt: Histidines can simultaneously hydrogen-bond to a phosphate and coordinate with an alkali metal ion to neutralize phosphate charge, thereby facilitating multidentate bonds to lipid headgroups in order to generate saddle-splay curvature, a prerequisite to pore formation. A comparison among Na , K , and Cs indicates that histidine-mediated salt tolerance is ion specific. We conclude that histidine plays a unique role in enabling protein/peptide-membrane interactions that occur in marine or other high-salt environment.
抗菌肽 (AMPs) 通过静电结合和膜重塑优先穿透原核细胞膜。由于静电屏蔽增加，高盐会极大地抑制这种作用，因此令人困惑的是，海洋 AMP 如何可能发挥作用。我们以鱼素-1 为模型系统进行了检查，鱼素-1 是一种富含组氨酸的海洋 AMP，结果表明，离子-组氨酸相互作用在高盐下的膜重塑中发挥了意想不到的作用：组氨酸可以同时与磷酸基团形成氢键，并与碱金属离子配位以中和磷酸基团的电荷，从而促进与脂质头基的多齿键合，以产生马鞍式扭曲，这是形成孔的先决条件。Na 、K 和 Cs 的比较表明，组氨酸介导的耐盐性是离子特异性的。我们得出结论，组氨酸在使发生在海洋或其他高盐环境中的蛋白质/肽-膜相互作用中发挥了独特的作用。
