Temporin L and aurein 2.5 have identical conformations but subtly distinct membrane and antibacterial activities.

Sci Rep 2019 Jul 29;9(1):10934. Epub 2019 Jul 29.

Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Science, King's College London, Franklin-Wilkins Building, 150 Stamford Street, London, SE1 9NH, United Kingdom.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-019-47327-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6662694PMC
July 2019
1 Read

Publication Analysis

Top Keywords

temporin aurein
12
spectrum activity
12
α-helix conformations
8
plasma membrane
8
ability form
8
bacterial plasma
8
model membranes
8
amphipathic α-helix
8
secondary amphipathic
8
membrane
5
amps
5
activity potency
4
potency amps
4
provide explanation
4
conformations spectrum
4
cationic amp
4
varies considerably
4
distinguishing amps
4
determinant ability
4
considerably distinguishing
4

References

(Supplied by CrossRef)

DI Andersson et al.
Drug Resist. Update. 2016

M Zasloff et al.
Nature. 2002

A Giuliani et al.
Cell. Mol. Life Sci. 2008

RE Hancock et al.
Trends Microbiol. 2000

EF Haney et al.
Biopolymers. 2013

H Jenssen et al.
Clin. Microbiol. Rev. 2006

N Malanovic et al.
Biochim. Biophys. Acta 2016

LT Nguyen et al.
Trends Biotechnol. 2011

S-BTA Amos et al.
Sci. Rep. 2016

J Kozlowska et al.
PLoS Pathog 2014

Similar Publications