Advanced

Role of aromatic amino acids in lipopolysaccharide and membrane interactions of antimicrobial peptides for use in plant disease control

Datta, Aritreyee; Bhattacharyya, Dipita; Singh, Shalini; Ghosh, Anirban; Schmidtchen, Artur LU ; Malmsten, Martin and Bhunia, Anirban (2016) In Journal of Biological Chemistry 291(25). p.13301-13317
Abstract

KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYT-LR), the representative sequence of helix D of heparin co-factor II, was demonstrated to be potent against agronomically important Gram-negative plant pathogens Xanthomonas vesicatoria and Xanthomonas oryzae, capable of inhibiting disease symptoms in detached tomato leaves. NMR studies in the presence of lipopolysaccharide provided structural insights into the mechanisms underlying this, notably in relationship to outer membrane permeabilization. The three-dimensional solution structure of KYE28 in LPS is characterized by an N-terminal helical segment, an intermediate loop followed by another short helical stretch, and an extended C terminus. The two termini are in close proximity to each other via... (More)

KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYT-LR), the representative sequence of helix D of heparin co-factor II, was demonstrated to be potent against agronomically important Gram-negative plant pathogens Xanthomonas vesicatoria and Xanthomonas oryzae, capable of inhibiting disease symptoms in detached tomato leaves. NMR studies in the presence of lipopolysaccharide provided structural insights into the mechanisms underlying this, notably in relationship to outer membrane permeabilization. The three-dimensional solution structure of KYE28 in LPS is characterized by an N-terminal helical segment, an intermediate loop followed by another short helical stretch, and an extended C terminus. The two termini are in close proximity to each other via aromatic packing interactions, whereas the positively charged residues form an exterior polar shell. To further demonstrate the importance of the aromatic residues for this, a mutant peptide KYE28A, with Ala substitutions at Phe11 , Phe19 , Phe23 , and Tyr25 was designed, which showed attenuated antimicrobial activity at high salt concentrations, as well as lower membrane disruption and LPS binding abilities compared with KYE28. In contrast to KYE28, KYE28A adopted an extended helical structure in LPS with extended N and C termini. Aromatic packing interactions were completely lost, although hydrophobic interaction between the side chains of hydrophobic residues were still partly retained, imparting an amphipathic character and explaining its residual antimicrobial activity and LPS binding as observed from ellipsometry and isothermal titration calorimetry. We thus present key structural aspects of KYE28, constituting an aromatic zipper, of potential importance for the development of novel plant protection agents and therapeutic agents.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
291
issue
25
pages
17 pages
publisher
ASBMB
external identifiers
  • scopus:84975045631
ISSN
0021-9258
DOI
10.1074/jbc.M116.719575
language
English
LU publication?
yes
id
123dc658-c358-4664-b3dc-874dfedc873b
date added to LUP
2017-01-20 14:23:48
date last changed
2017-11-19 04:36:53
@article{123dc658-c358-4664-b3dc-874dfedc873b,
  abstract     = {<p>KYE28 (KYEITTIHNLFRKLTHRLFRRNFGYT-LR), the representative sequence of helix D of heparin co-factor II, was demonstrated to be potent against agronomically important Gram-negative plant pathogens Xanthomonas vesicatoria and Xanthomonas oryzae, capable of inhibiting disease symptoms in detached tomato leaves. NMR studies in the presence of lipopolysaccharide provided structural insights into the mechanisms underlying this, notably in relationship to outer membrane permeabilization. The three-dimensional solution structure of KYE28 in LPS is characterized by an N-terminal helical segment, an intermediate loop followed by another short helical stretch, and an extended C terminus. The two termini are in close proximity to each other via aromatic packing interactions, whereas the positively charged residues form an exterior polar shell. To further demonstrate the importance of the aromatic residues for this, a mutant peptide KYE28A, with Ala substitutions at Phe11 , Phe19 , Phe23 , and Tyr25 was designed, which showed attenuated antimicrobial activity at high salt concentrations, as well as lower membrane disruption and LPS binding abilities compared with KYE28. In contrast to KYE28, KYE28A adopted an extended helical structure in LPS with extended N and C termini. Aromatic packing interactions were completely lost, although hydrophobic interaction between the side chains of hydrophobic residues were still partly retained, imparting an amphipathic character and explaining its residual antimicrobial activity and LPS binding as observed from ellipsometry and isothermal titration calorimetry. We thus present key structural aspects of KYE28, constituting an aromatic zipper, of potential importance for the development of novel plant protection agents and therapeutic agents.</p>},
  author       = {Datta, Aritreyee and Bhattacharyya, Dipita and Singh, Shalini and Ghosh, Anirban and Schmidtchen, Artur and Malmsten, Martin and Bhunia, Anirban},
  issn         = {0021-9258},
  language     = {eng},
  month        = {06},
  number       = {25},
  pages        = {13301--13317},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Role of aromatic amino acids in lipopolysaccharide and membrane interactions of antimicrobial peptides for use in plant disease control},
  url          = {http://dx.doi.org/10.1074/jbc.M116.719575},
  volume       = {291},
  year         = {2016},
}