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

被引：10

作者：

Xian, Wujing ^{[1
]}

Hennefarth, Matthew R. ^{[2
]}

Lee, Michelle W. ^{[1
]}

Do, Tran ^{[1
]}

Lee, Ernest Y. ^{[1
]}

Alexandrova, Anastassia N. ^{[2
,3
]}

Wong, Gerard C. L. ^{[1
,3
]}

机构：

[1] Univ Calif Los Angeles, Dept Bioengn, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Calif Nano Syst Inst, Los Angeles, CA 90095 USA

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2022年 / 61卷 / 25期

基金：

美国国家卫生研究院;

关键词：

Antimicrobial Peptide; Histidine; Hofmeister Series; Ion-Specific; Membrane; CELL-PENETRATING PEPTIDES; RICH PEPTIDES; PISCIDIN; 3; LIPID-BILAYERS; X-RAY; MEMBRANE; MECHANISM; ARGININE; ENTRY; OLIGOARGININE;

D O I：

10.1002/anie.202108501

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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.

引用

页数：8