1XKM

NMR structure of antimicrobial peptide distinctin in water

1XKM の概要

• エントリーDOI: 10.2210/pdb1xkm/pdb
• NMR情報: BMRB: 6499
• 分子名称: Distinctin chain A, Distinctin chain B (2 entities in total)
• 機能のキーワード: pore-forming peptide, heterodimer, homodimer, disulfide, four-helix bundle, antibiotic
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 10985.28

構造登録者

Amodeo, P.,Raimondo, D.,Andreotti, G.,Motta, A.,Scaloni, A. (登録日: 2004-09-29, 公開日: 2005-04-05, 最終更新日: 2024-10-23)

主引用文献

Raimondo, D.,Andreotti, G.,Saint, N.,Amodeo, P.,Renzone, G.,Sanseverino, M.,Zocchi, I.,Molle, G.,Motta, A.,Scaloni, A.
A folding-dependent mechanism of antimicrobial peptide resistance to degradation unveiled by solution structure of distinctin.
Proc.Natl.Acad.Sci.Usa, 102:6309-6314, 2005

PubMed Abstract: Many bioactive peptides, presenting an unstructured conformation in aqueous solution, are made resistant to degradation by posttranslational modifications. Here, we describe how molecular oligomerization in aqueous solution can generate a still unknown transport form for amphipathic peptides, which is more compact and resistant to proteases than forms related to any possible monomer. This phenomenon emerged from 3D structure, function, and degradation properties of distinctin, a heterodimeric antimicrobial compound consisting of two peptide chains linked by a disulfide bond. After homodimerization in water, this peptide exhibited a fold consisting of a symmetrical full-parallel four-helix bundle, with a well secluded hydrophobic core and exposed basic residues. This fold significantly stabilizes distinctin against proteases compared with other linear amphipathic peptides, without affecting its antimicrobial, hemolytic, and ion-channel formation properties after membrane interaction. This full-parallel helical orientation represents a perfect compromise between formation of a stable structure in water and requirement of a drastic structural rearrangement in membranes to elicit antimicrobial potential. Thus, distinctin can be claimed as a prototype of a previously unrecognized class of antimicrobial derivatives. These results suggest a critical revision of the role of peptide oligomerization whenever solubility or resistance to proteases is known to affect biological properties.

PubMed: 15840728
DOI: 10.1073/pnas.0409004102

実験手法

SOLUTION NMR