title: A kinked antimicrobial peptide from Bombina maxima. II. Behavior in phospholipid bilayers.
abstract: The preceding contribution by Toke et al. has studied the structure of the cationic antimicrobial peptide maximin-4 in detergent micelles and in organic solvent, revealing a different kink angle and side-chain interactions in the two different environments. Here, we have examined the same peptide in lipid bilayers using oriented circular dichroism (OCD) and solid-state (15)N nuclear magnetic resonance (NMR) in aligned samples. OCD showed that maximin-4 is helical and adopts an oblique alignment in the membrane, and lacks the characteristic realignment response that is often observed for amphipathic α-helical peptides at a peptide:lipid ratio between 1:100 and 1:20. Solid-state (15)N-NMR experiments suggest that maximin-4 also remains unaffected by lipid charge and temperature. Analyzing (15)N labels in positions Ala12, Ala13, and Leu14, an oblique tilt angle of the N-terminal helix of ~130° relative to the membrane normal was found, in good agreement with the amphiphilic profile of this segment. An additional constraint at Ala22 in the C-terminal segment is found to be compatible with a continuous α-helix, but unfavorable side-chain interactions make this solution unlikely. Instead, a kink at Gly16 seems fully compatible with all known constraints and with the biophysical expectations in the membrane-bound state, given the liquid-state NMR structures. It thus seems that the flexible kink in maximin-4 allows the two helical segments to adjust to the local environment. The irregular amphiphilic profile and the resulting versatility in shape might explain why maximin-4 lacks the realignment response that has been characteristically observed for many related frog peptides forming straight amphipathic α-helices.
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Biological Interfaces (IBG-2), P.O. Box 3640, 76021 Karlsruhe, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Heinzmann
authors.forename: Stephan L
authors.initials: SL
authors.lastname: Grage
authors.forename: Constantin
authors.initials: C
authors.lastname: Schalck
authors.forename: Jochen
authors.initials: J
authors.lastname: Bürck
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Bánóczi
authors.forename: Orsolya
authors.initials: O
authors.lastname: Toke
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D001001:Anura / Q000378:metabolism*; D002942:Circular Dichroism / Q000379:methods; D008051:Lipid Bilayers / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008969:Molecular Sequence Data; D010743:Phospholipids / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D017433:Protein Structure, Secondary; D013696:Temperature
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010743:Phospholipids