6GS9

NMR structure of aurein 2.5 in SDS micelles

6GS9 の概要

• エントリーDOI: 10.2210/pdb6gs9/pdb
• NMR情報: BMRB: 34284
• 分子名称: Aurein 2.5 (1 entity in total)
• 機能のキーワード: amp, aurein 2.5, antimicrobial protein, sds micelle
• 由来する生物種: Litoria aurea (green and golden bell frog)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 1651.99

構造登録者

Manzo, G.,Mason, J.A. (登録日: 2018-06-13, 公開日: 2018-07-18, 最終更新日: 2024-06-19)

主引用文献

Manzo, G.,Ferguson, P.M.,Hind, C.K.,Clifford, M.,Gustilo, V.B.,Ali, H.,Bansal, S.S.,Bui, T.T.,Drake, A.F.,Atkinson, R.A.,Sutton, J.M.,Lorenz, C.D.,Phoenix, D.A.,Mason, A.J.
Temporin L and aurein 2.5 have identical conformations but subtly distinct membrane and antibacterial activities.
Sci Rep, 9:10934-10934, 2019

PubMed Abstract: Frogs such as Rana temporaria and Litoria aurea secrete numerous closely related antimicrobial peptides (AMPs) as an effective chemical dermal defence. Damage or penetration of the bacterial plasma membrane is considered essential for AMP activity and such properties are commonly ascribed to their ability to form secondary amphipathic, α-helix conformations in membrane mimicking milieu. Nevertheless, despite the high similarity in physical properties and preference for adopting such conformations, the spectrum of activity and potency of AMPs often varies considerably. Hence distinguishing apparently similar AMPs according to their behaviour in, and effects on, model membranes will inform understanding of primary-sequence-specific antimicrobial mechanisms. Here we use a combination of molecular dynamics simulations, circular dichroism and patch-clamp to investigate the basis for differing anti-bacterial activities in representative AMPs from each species; temporin L and aurein 2.5. Despite adopting near identical, α-helix conformations in the steady-state in a variety of membrane models, these two AMPs can be distinguished both in vitro and in silico based on their dynamic interactions with model membranes, notably their differing conformational flexibility at the N-terminus, ability to form higher order aggregates and the characteristics of induced ion conductance. Taken together, these differences provide an explanation of the greater potency and broader antibacterial spectrum of activity of temporin L over aurein 2.5. Consequently, while the secondary amphipathic, α-helix conformation is a key determinant of the ability of a cationic AMP to penetrate and disrupt the bacterial plasma membrane, the exact mechanism, potency and spectrum of activity is determined by precise structural and dynamic contributions from specific residues in each AMP sequence.

PubMed: 31358802
DOI: 10.1038/s41598-019-47327-w

実験手法

SOLUTION NMR