Histidine‐Mediated Ion Specific Effects Enable Salt Tolerance of a Pore‐Forming Marine Antimicrobial Peptide

Abstract

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.

Self-Assembled DNA Machine and Selective Complexation Recognition Enable Rapid Homogeneous Portable Quantification of Lung Cancer CTCs

“…Metal ions are prevalent in the biological world, playing a crucial role in applications ranging from bioanalysis to medical treatments. It is now understood that metal cations such as Cu 2+ , Ag + , Hg 2+ , Cd 2+ , Pd 2+ , and others exhibit strong coordination with functional groups like thiol, carboxylate, and amine groups of cysteine (Cys) [ 1 , 2 ], the imidazole group of histidine (His) [ 3 , 4 ], as well as the phosphate of pyrophosphate (PPi) [ 5 ]. These interactions have led to the development of a wide array of sensing platforms.…”