title: Spontaneous formation of structurally diverse membrane channel architectures from a single antimicrobial peptide.
abstract: Many antimicrobial peptides (AMPs) selectively target and form pores in microbial membranes. However, the mechanisms of membrane targeting, pore formation and function remain elusive. Here we report an experimentally guided unbiased simulation methodology that yields the mechanism of spontaneous pore assembly for the AMP maculatin at atomic resolution. Rather than a single pore, maculatin forms an ensemble of structurally diverse temporarily functional low-oligomeric pores, which mimic integral membrane protein channels in structure. These pores continuously form and dissociate in the membrane. Membrane permeabilization is dominated by hexa-, hepta- and octamers, which conduct water, ions and small dyes. Pores form by consecutive addition of individual helices to a transmembrane helix or helix bundle, in contrast to current poration models. The diversity of the pore architectures-formed by a single sequence-may be a key feature in preventing bacterial resistance and could explain why sequence-function relationships in AMPs remain elusive.
authors.affiliation: Institute of Natural Sciences, Shanghai Jiao-Tong University, 800 Dongchuan Road, Shanghai 200240, China.|Department of Physics and Astronomy, Shanghai Jiao-Tong University, 800 Dongchuan Road, Shanghai 200240, China.|Institute of NanoBioTechnology, Johns Hopkins University, 204C Schaffer Hall, 3400 North Charles Street, Baltimore, Maryland 21218-2681, USA.
authors.forename: Yukun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of NanoBioTechnology, Johns Hopkins University, 204C Schaffer Hall, 3400 North Charles Street, Baltimore, Maryland 21218-2681, USA.|Department of Materials Science and Engineering, Johns Hopkins University, 204C Schaffer Hall, 3400 North Charles Street, Baltimore, Maryland 21218-2681, USA.
authors.forename: Charles H
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Institute of Natural Sciences, Shanghai Jiao-Tong University, 800 Dongchuan Road, Shanghai 200240, China.|Department of Mathematics, Shanghai Jiao-Tong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Institute of NanoBioTechnology, Johns Hopkins University, 204C Schaffer Hall, 3400 North Charles Street, Baltimore, Maryland 21218-2681, USA.|Department of Materials Science and Engineering, Johns Hopkins University, 204C Schaffer Hall, 3400 North Charles Street, Baltimore, Maryland 21218-2681, USA.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Ulmschneider
authors.affiliation: Institute of Natural Sciences, Shanghai Jiao-Tong University, 800 Dongchuan Road, Shanghai 200240, China.|Department of Physics and Astronomy, Shanghai Jiao-Tong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Jakob P
authors.initials: JP
authors.lastname: Ulmschneider
mesh_terms: D000595:Amino Acid Sequence; D029845:Amphibian Proteins / Q000138:chemical synthesis / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D055550:Protein Stability; D013816:Thermodynamics
chemical_list: D029845:Amphibian Proteins; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; C113499:maculatin-1.1 protein, Litoria