Cargando…
Spectroscopic and Computational Study of Melittin, Cecropin A, and the Hybrid Peptide CM15
[Image: see text] Antimicrobial peptides (AMPs), such as cecropin A from silk moth, are key components of the innate immune system. They are effective defensive weapons against invading pathogens, yet they do not target host eukaryotic cells. In contrast, peptide toxins, such as honeybee melittin, a...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American
Chemical Society
2012
|
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434763/ https://www.ncbi.nlm.nih.gov/pubmed/22845179 http://dx.doi.org/10.1021/jp304021t |
_version_ | 1782242463205818368 |
---|---|
author | Schlamadinger, Diana E. Wang, Yi McCammon, J. Andrew Kim, Judy E. |
author_facet | Schlamadinger, Diana E. Wang, Yi McCammon, J. Andrew Kim, Judy E. |
author_sort | Schlamadinger, Diana E. |
collection | PubMed |
description | [Image: see text] Antimicrobial peptides (AMPs), such as cecropin A from silk moth, are key components of the innate immune system. They are effective defensive weapons against invading pathogens, yet they do not target host eukaryotic cells. In contrast, peptide toxins, such as honeybee melittin, are nondiscriminating and target both eukaryotic and prokaryotic cells. An AMP-toxin hybrid peptide that is composed of cecropin A and melittin (CM15) improves upon the antimicrobial activity of cecropin A without displaying the nonspecific, hemolytic properties of melittin. Here we report fluorescence and UV resonance Raman spectra of melittin, cecropin A, and CM15 with the goal of elucidating peptide-membrane interactions that help guide specificity. We have probed the potency for membrane disruption, local environment and structure of the single tryptophan residue, backbone conformation near the peptide hinge, and amide backbone structure of the peptides in lipid environments that mimic eukaryotic and prokaryotic membranes. These experimental results suggest that melittin inserts deeply into the bilayer, whereas cecropin A remains localized to the lipid headgroup region. A surprising finding is that CM15 is a potent membrane-disruptor despite its largely unfolded conformation. A molecular dynamics analysis complements these data and demonstrates the ability of CM15 to associate favorably with membranes as an unfolded peptide. This combined experimental–computational study suggests that new models for peptide–membrane interactions should be considered. |
format | Online Article Text |
id | pubmed-3434763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | American
Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-34347632012-09-06 Spectroscopic and Computational Study of Melittin, Cecropin A, and the Hybrid Peptide CM15 Schlamadinger, Diana E. Wang, Yi McCammon, J. Andrew Kim, Judy E. J Phys Chem B [Image: see text] Antimicrobial peptides (AMPs), such as cecropin A from silk moth, are key components of the innate immune system. They are effective defensive weapons against invading pathogens, yet they do not target host eukaryotic cells. In contrast, peptide toxins, such as honeybee melittin, are nondiscriminating and target both eukaryotic and prokaryotic cells. An AMP-toxin hybrid peptide that is composed of cecropin A and melittin (CM15) improves upon the antimicrobial activity of cecropin A without displaying the nonspecific, hemolytic properties of melittin. Here we report fluorescence and UV resonance Raman spectra of melittin, cecropin A, and CM15 with the goal of elucidating peptide-membrane interactions that help guide specificity. We have probed the potency for membrane disruption, local environment and structure of the single tryptophan residue, backbone conformation near the peptide hinge, and amide backbone structure of the peptides in lipid environments that mimic eukaryotic and prokaryotic membranes. These experimental results suggest that melittin inserts deeply into the bilayer, whereas cecropin A remains localized to the lipid headgroup region. A surprising finding is that CM15 is a potent membrane-disruptor despite its largely unfolded conformation. A molecular dynamics analysis complements these data and demonstrates the ability of CM15 to associate favorably with membranes as an unfolded peptide. This combined experimental–computational study suggests that new models for peptide–membrane interactions should be considered. American Chemical Society 2012-07-30 2012-09-06 /pmc/articles/PMC3434763/ /pubmed/22845179 http://dx.doi.org/10.1021/jp304021t Text en Copyright © 2012 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. |
spellingShingle | Schlamadinger, Diana E. Wang, Yi McCammon, J. Andrew Kim, Judy E. Spectroscopic and Computational Study of Melittin, Cecropin A, and the Hybrid Peptide CM15 |
title | Spectroscopic and Computational
Study of Melittin,
Cecropin A, and the Hybrid Peptide CM15 |
title_full | Spectroscopic and Computational
Study of Melittin,
Cecropin A, and the Hybrid Peptide CM15 |
title_fullStr | Spectroscopic and Computational
Study of Melittin,
Cecropin A, and the Hybrid Peptide CM15 |
title_full_unstemmed | Spectroscopic and Computational
Study of Melittin,
Cecropin A, and the Hybrid Peptide CM15 |
title_short | Spectroscopic and Computational
Study of Melittin,
Cecropin A, and the Hybrid Peptide CM15 |
title_sort | spectroscopic and computational
study of melittin,
cecropin a, and the hybrid peptide cm15 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434763/ https://www.ncbi.nlm.nih.gov/pubmed/22845179 http://dx.doi.org/10.1021/jp304021t |
work_keys_str_mv | AT schlamadingerdianae spectroscopicandcomputationalstudyofmelittincecropinaandthehybridpeptidecm15 AT wangyi spectroscopicandcomputationalstudyofmelittincecropinaandthehybridpeptidecm15 AT mccammonjandrew spectroscopicandcomputationalstudyofmelittincecropinaandthehybridpeptidecm15 AT kimjudye spectroscopicandcomputationalstudyofmelittincecropinaandthehybridpeptidecm15 |