Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins
In this study, dodecapeptide cathelicidins were shown to be widespread antimicrobial peptides among the Cetruminantia clade. In particular, we investigated the dodecapeptide from the domestic goat Capra hircus, designated as ChDode and its unique ortholog from the sperm whale Physeter catodon (PcDod...
Published in: | Frontiers in Microbiology |
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Language: | English |
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Frontiers Media S.A.
2021
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Online Access: | https://doi.org/10.3389/fmicb.2021.725526 https://doaj.org/article/5bdff750a9d0479a9f0fb4bd9d62559d |
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ftdoajarticles:oai:doaj.org/article:5bdff750a9d0479a9f0fb4bd9d62559d 2023-05-15T18:26:51+02:00 Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins Ilia A. Bolosov Pavel V. Panteleev Sergei V. Sychev Stanislav V. Sukhanov Pavel A. Mironov Mikhail Yu. Myshkin Zakhar O. Shenkarev Tatiana V. Ovchinnikova 2021-08-01T00:00:00Z https://doi.org/10.3389/fmicb.2021.725526 https://doaj.org/article/5bdff750a9d0479a9f0fb4bd9d62559d EN eng Frontiers Media S.A. https://www.frontiersin.org/articles/10.3389/fmicb.2021.725526/full https://doaj.org/toc/1664-302X 1664-302X doi:10.3389/fmicb.2021.725526 https://doaj.org/article/5bdff750a9d0479a9f0fb4bd9d62559d Frontiers in Microbiology, Vol 12 (2021) antimicrobial peptide cathelicidin dodecapeptide goat synergy NMR Microbiology QR1-502 article 2021 ftdoajarticles https://doi.org/10.3389/fmicb.2021.725526 2022-12-31T10:25:06Z In this study, dodecapeptide cathelicidins were shown to be widespread antimicrobial peptides among the Cetruminantia clade. In particular, we investigated the dodecapeptide from the domestic goat Capra hircus, designated as ChDode and its unique ortholog from the sperm whale Physeter catodon (PcDode). ChDode contains two cysteine residues, while PcDode consists of two dodecapeptide building blocks and contains four cysteine residues. The recombinant analogs of the peptides were obtained by heterologous expression in Escherichia coli cells. The structures of the peptides were studied by circular dichroism (CD), FTIR, and NMR spectroscopy. It was demonstrated that PcDode adopts a β-hairpin structure in water and resembles β-hairpin antimicrobial peptides, while ChDode forms a β-structural antiparallel covalent dimer, stabilized by two intermonomer disulfide bonds. Both peptides reveal a significant right-handed twist about 200 degrees per 8 residues. In DPC micelles ChDode forms flat β-structural tetramers by antiparallel non-covalent association of the dimers. The tetramers incorporate into the micelles in transmembrane orientation. Incorporation into the micelles and dimerization significantly diminished the amplitude of backbone motions of ChDode at the picosecond-nanosecond timescale. When interacting with negatively charged membranes containing phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), the ChDode peptide adopted similar oligomeric structure and was capable to form ion-conducting pores without membrane lysis. Despite modest antibacterial activity of ChDode, a considerable synergistic effect of this peptide in combination with another goat cathelicidin – the α-helical peptide ChMAP-28 was observed. This effect is based on an increase in permeability of bacterial membranes. In turn, this mechanism can lead to an increase in the efficiency of the combined action of the synergistic pair ChMAP-28 with the Pro-rich peptide mini-ChBac7.5Nα targeting the bacterial ribosome. Article in Journal/Newspaper Sperm whale Directory of Open Access Journals: DOAJ Articles Catodon ENVELOPE(-59.966,-59.966,-63.500,-63.500) Frontiers in Microbiology 12 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
antimicrobial peptide cathelicidin dodecapeptide goat synergy NMR Microbiology QR1-502 |
spellingShingle |
antimicrobial peptide cathelicidin dodecapeptide goat synergy NMR Microbiology QR1-502 Ilia A. Bolosov Pavel V. Panteleev Sergei V. Sychev Stanislav V. Sukhanov Pavel A. Mironov Mikhail Yu. Myshkin Zakhar O. Shenkarev Tatiana V. Ovchinnikova Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins |
topic_facet |
antimicrobial peptide cathelicidin dodecapeptide goat synergy NMR Microbiology QR1-502 |
description |
In this study, dodecapeptide cathelicidins were shown to be widespread antimicrobial peptides among the Cetruminantia clade. In particular, we investigated the dodecapeptide from the domestic goat Capra hircus, designated as ChDode and its unique ortholog from the sperm whale Physeter catodon (PcDode). ChDode contains two cysteine residues, while PcDode consists of two dodecapeptide building blocks and contains four cysteine residues. The recombinant analogs of the peptides were obtained by heterologous expression in Escherichia coli cells. The structures of the peptides were studied by circular dichroism (CD), FTIR, and NMR spectroscopy. It was demonstrated that PcDode adopts a β-hairpin structure in water and resembles β-hairpin antimicrobial peptides, while ChDode forms a β-structural antiparallel covalent dimer, stabilized by two intermonomer disulfide bonds. Both peptides reveal a significant right-handed twist about 200 degrees per 8 residues. In DPC micelles ChDode forms flat β-structural tetramers by antiparallel non-covalent association of the dimers. The tetramers incorporate into the micelles in transmembrane orientation. Incorporation into the micelles and dimerization significantly diminished the amplitude of backbone motions of ChDode at the picosecond-nanosecond timescale. When interacting with negatively charged membranes containing phosphatidylethanolamine (PE) and phosphatidylglycerol (PG), the ChDode peptide adopted similar oligomeric structure and was capable to form ion-conducting pores without membrane lysis. Despite modest antibacterial activity of ChDode, a considerable synergistic effect of this peptide in combination with another goat cathelicidin – the α-helical peptide ChMAP-28 was observed. This effect is based on an increase in permeability of bacterial membranes. In turn, this mechanism can lead to an increase in the efficiency of the combined action of the synergistic pair ChMAP-28 with the Pro-rich peptide mini-ChBac7.5Nα targeting the bacterial ribosome. |
format |
Article in Journal/Newspaper |
author |
Ilia A. Bolosov Pavel V. Panteleev Sergei V. Sychev Stanislav V. Sukhanov Pavel A. Mironov Mikhail Yu. Myshkin Zakhar O. Shenkarev Tatiana V. Ovchinnikova |
author_facet |
Ilia A. Bolosov Pavel V. Panteleev Sergei V. Sychev Stanislav V. Sukhanov Pavel A. Mironov Mikhail Yu. Myshkin Zakhar O. Shenkarev Tatiana V. Ovchinnikova |
author_sort |
Ilia A. Bolosov |
title |
Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins |
title_short |
Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins |
title_full |
Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins |
title_fullStr |
Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins |
title_full_unstemmed |
Dodecapeptide Cathelicidins of Cetartiodactyla: Structure, Mechanism of Antimicrobial Action, and Synergistic Interaction With Other Cathelicidins |
title_sort |
dodecapeptide cathelicidins of cetartiodactyla: structure, mechanism of antimicrobial action, and synergistic interaction with other cathelicidins |
publisher |
Frontiers Media S.A. |
publishDate |
2021 |
url |
https://doi.org/10.3389/fmicb.2021.725526 https://doaj.org/article/5bdff750a9d0479a9f0fb4bd9d62559d |
long_lat |
ENVELOPE(-59.966,-59.966,-63.500,-63.500) |
geographic |
Catodon |
geographic_facet |
Catodon |
genre |
Sperm whale |
genre_facet |
Sperm whale |
op_source |
Frontiers in Microbiology, Vol 12 (2021) |
op_relation |
https://www.frontiersin.org/articles/10.3389/fmicb.2021.725526/full https://doaj.org/toc/1664-302X 1664-302X doi:10.3389/fmicb.2021.725526 https://doaj.org/article/5bdff750a9d0479a9f0fb4bd9d62559d |
op_doi |
https://doi.org/10.3389/fmicb.2021.725526 |
container_title |
Frontiers in Microbiology |
container_volume |
12 |
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1766208819310886912 |