2LM8

Structure, Activity and Interactions of the Cysteine Deleted Analog of Tachyplesin-1 with Lipopolysaccharide Micelles

2LM8 の概要

• エントリーDOI: 10.2210/pdb2lm8/pdb
• NMR情報: BMRB: 18102
• 分子名称: CDT-LPS (1 entity in total)
• 機能のキーワード: antimicrobial protein
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1862.24

構造登録者

Joshi, M.,Bhattacharjya, S.,Saravanan, R. (登録日: 2011-11-25, 公開日: 2012-04-25, 最終更新日: 2024-05-15)

主引用文献

Saravanan, R.,Mohanram, H.,Joshi, M.,Domadia, P.N.,Torres, J.,Ruedl, C.,Bhattacharjya, S.
Structure, activity and interactions of the cysteine deleted analog of tachyplesin-1 with lipopolysaccharide micelle: Mechanistic insights into outer-membrane permeabilization and endotoxin neutralization.
Biochim.Biophys.Acta, 1818:1613-1624, 2012

PubMed Abstract: Tachyplesin-1, a disulfide stabilized beta-hairpin antimicrobial peptide, can be found at the hemocytes of horse shoe crab Tachypleus tridentatus. A cysteine deleted linear analog of tachyplesin-1 or CDT (KWFRVYRGIYRRR-NH2) contains a broad spectrum of bactericidal activity with a reduced hemolytic property. The bactericidal activity of CDT stems from selective interactions with the negatively charged lipids including LPS. In this work, CDT-LPS interactions were investigated using NMR spectroscopy, optical spectroscopy and functional assays. We found that CDT neutralized LPS and disrupted permeability barrier of the outer membrane. Zeta potential and ITC studies demonstrated charge compensation and hydrophobic interactions of CDT with the LPS-outer membrane, respectively. Secondary structure of the peptide was probed by CD and FT-IR experiments indicating beta-strands and/or beta-turn conformations in the LPS micelle. An ensemble of structures, determined in LPS micelle by NMR, revealed a beta-hairpin like topology of the CDT peptide that was typified by an extended cationic surface and a relatively shorter segment of hydrophobic region. Interestingly, at the non-polar face, residue R11 was found to be in a close proximity to the indole ring of W2, suggesting a cation-n type interactions. Further, saturation transfer difference (STD) NMR studies established intimate contacts among the aromatic and cationic residues of CDT with the LPS micelle. Fluorescence and dynamic light scattering experiments demonstrated that CDT imparted structural destabilization to the aggregated states of LPS. Collectively, atomic resolution structure and interactions of CDT with the outer membrane-LPS could be exploited for developing potent broad spectrum antimicrobial and anti-sepsis agents.

PubMed: 22464970
DOI: 10.1016/j.bbamem.2012.03.015

実験手法

SOLUTION NMR