2KJO

pH dependent structures of LAH4 in micellar environment: mode of acting

2KJO の概要

• エントリーDOI: 10.2210/pdb2kjo/pdb
• 関連するPDBエントリー: 2KJN
• NMR情報: BMRB: 16333
• 分子名称: lah4 (1 entity in total)
• 機能のキーワード: lah4 neutral, de novo protein
• 由来する生物種: artificial gene
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2787.52

構造登録者

Georgescu, J.,Bechinger, B. (登録日: 2009-06-04, 公開日: 2010-06-23, 最終更新日: 2024-05-08)

主引用文献

Georgescu, J.,Munhoz, V.H.,Bechinger, B.
NMR structures of the histidine-rich peptide LAH4 in micellar environments: membrane insertion, pH-dependent mode of antimicrobial action, and DNA transfection.
Biophys.J., 99:2507-2515, 2010

PubMed Abstract: The LAH4 family of histidine-rich peptides exhibits potent antimicrobial and DNA transfection activities, both of which require interactions with cellular membranes. The bilayer association of the peptides has been shown to be strongly pH-dependent, with in-planar alignments under acidic conditions and transmembrane orientations when the histidines are discharged. Therefore, we investigated the pH- and temperature-dependent conformations of LAH4 in DPC micellar solutions and in a TFE/PBS solvent mixture. In the presence of detergent and at pH 4.1, LAH4 adopts helical conformations between residues 9 and 24 concomitantly with a high hydrophobic moment. At pH 6.1, a helix-loop-helix structure forms with a hinge encompassing residues His¹⁰-Ala¹³. The data suggest that the high density of histidine residues and the resulting electrostatic repulsion lead to both a decrease in the pK values of the histidines and a less stable α-helical conformation of this region. The hinged structure at pH 6.1 facilitates membrane anchoring and insertion. At pH 7.8, the histidines are uncharged and an extended helical conformation including residues 4-21 is again obtained. LAH4 thus exhibits a high degree of conformational plasticity. The structures provide a stroboscopic view of the conformational changes that occur during membrane insertion, and are discussed in the context of antimicrobial activity and DNA transfection.

PubMed: 20959091
DOI: 10.1016/j.bpj.2010.05.038

実験手法

SOLUTION NMR