2PCO

Spatial Structure and Membrane Permeabilization for Latarcin-1, a Spider Antimicrobial Peptide

2PCO の概要

• エントリーDOI: 10.2210/pdb2pco/pdb
• 関連するPDBエントリー: 2G9P
• NMR情報: BMRB: 7402
• 分子名称: Latarcin-1 (1 entity in total)
• 機能のキーワード: continuous helix, toxin
• 細胞内の位置: Secreted: Q1ELT9
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 3213.03

構造登録者

Dubovskii, P.V.,Volynsky, P.E.,Polyansky, A.A.,Chupin, V.V.,Efremov, R.G.,Arseniev, A.S. (登録日: 2007-03-30, 公開日: 2008-03-18, 最終更新日: 2024-05-22)

主引用文献

Dubovskii, P.V.,Volynsky, P.E.,Polyansky, A.A.,Karpunin, D.V.,Chupin, V.V.,Efremov, R.G.,Arseniev, A.S.
Three-dimensional structure/hydrophobicity of latarcins specifies their mode of membrane activity.
Biochemistry, 47:3525-3533, 2008

PubMed Abstract: Latarcins, linear peptides from the Lachesana tarabaevi spider venom, exhibit a broad-spectrum antimicrobial activity, likely acting on the bacterial cytoplasmic membrane. We study their spatial structures and interaction with model membranes by a combination of experimental and theoretical methods to reveal the structure-activity relationship. In this work, a 26 amino acid peptide, Ltc1, was investigated. Its spatial structure in detergent micelles was determined by (1)H nuclear magnetic resonance (NMR) and refined by Monte Carlo simulations in an implicit water-octanol slab. The Ltc1 molecule was found to form a straight uninterrupted amphiphilic helix comprising 8-23 residues. A dye-leakage fluorescent assay and (31)P NMR spectroscopy established that the peptide does not induce the release of fluorescent marker nor deteriorate the bilayer structure of the membranes. The voltage-clamp technique showed that Ltc1 induces the current fluctuations through planar membranes when the sign of the applied potential coincides with the one across the bacterial inner membrane. This implies that Ltc1 acts on the membranes via a specific mechanism, which is different from the carpet mode demonstrated by another latarcin, Ltc2a, featuring a helix-hinge-helix structure with a hydrophobicity gradient along the peptide chain. In contrast, the hydrophobic surface of the Ltc1 helix is narrow-shaped and extends with no gradient along the axis. We have also disclosed a number of peptides, structurally homologous to Ltc1 and exhibiting similar membrane activity. This indicates that the hydrophobic pattern of the Ltc1 helix and related antimicrobial peptides specifies their activity mechanism. The latter assumes the formation of variable-sized lesions, which depend upon the potential across the membrane.

PubMed: 18293934
DOI: 10.1021/bi702203w

実験手法

SOLUTION NMR