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The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions
Mammals protect themselves from inflammation triggered by microorganisms through secretion of antimicrobial peptides (AMPs). One mechanism by which AMPs kill bacterial cells is perforating their membranes. Membrane interactions and pore formation were investigated for α-helical AMPs leading to the f...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681987/ https://www.ncbi.nlm.nih.gov/pubmed/29164103 http://dx.doi.org/10.3389/fchem.2017.00086 |
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author | Zeth, Kornelius Sancho-Vaello, Enea |
author_facet | Zeth, Kornelius Sancho-Vaello, Enea |
author_sort | Zeth, Kornelius |
collection | PubMed |
description | Mammals protect themselves from inflammation triggered by microorganisms through secretion of antimicrobial peptides (AMPs). One mechanism by which AMPs kill bacterial cells is perforating their membranes. Membrane interactions and pore formation were investigated for α-helical AMPs leading to the formulation of three basic mechanistic models: the barrel stave, toroidal, and carpet model. One major drawback of these models is their simplicity. They do not reflect the real in vitro and in vivo conditions. To challenge and refine these models using a structure-based approach we set out to investigate how human cathelicidin (LL-37) and dermcidin (DCD) interact with membranes. Both peptides are α-helical and their structures have been solved at atomic resolution. DCD assembles in solution into a hexameric pre-channel complex before the actual membrane targeting and integration step can occur, and the complex follows a deviation of the barrel stave model. LL-37 interacts with lipids and shows the formation of oligomers generating fibril-like supramolecular structures on membranes. LL-37 further assembles into transmembrane pores with yet unknown structure expressing a deviation of the toroidal pore model. Both of their specific targeting mechanisms will be discussed in the context of the “old” models propagated in the literature. |
format | Online Article Text |
id | pubmed-5681987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56819872017-11-21 The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions Zeth, Kornelius Sancho-Vaello, Enea Front Chem Chemistry Mammals protect themselves from inflammation triggered by microorganisms through secretion of antimicrobial peptides (AMPs). One mechanism by which AMPs kill bacterial cells is perforating their membranes. Membrane interactions and pore formation were investigated for α-helical AMPs leading to the formulation of three basic mechanistic models: the barrel stave, toroidal, and carpet model. One major drawback of these models is their simplicity. They do not reflect the real in vitro and in vivo conditions. To challenge and refine these models using a structure-based approach we set out to investigate how human cathelicidin (LL-37) and dermcidin (DCD) interact with membranes. Both peptides are α-helical and their structures have been solved at atomic resolution. DCD assembles in solution into a hexameric pre-channel complex before the actual membrane targeting and integration step can occur, and the complex follows a deviation of the barrel stave model. LL-37 interacts with lipids and shows the formation of oligomers generating fibril-like supramolecular structures on membranes. LL-37 further assembles into transmembrane pores with yet unknown structure expressing a deviation of the toroidal pore model. Both of their specific targeting mechanisms will be discussed in the context of the “old” models propagated in the literature. Frontiers Media S.A. 2017-11-07 /pmc/articles/PMC5681987/ /pubmed/29164103 http://dx.doi.org/10.3389/fchem.2017.00086 Text en Copyright © 2017 Zeth and Sancho-Vaello. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Chemistry Zeth, Kornelius Sancho-Vaello, Enea The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions |
title | The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions |
title_full | The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions |
title_fullStr | The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions |
title_full_unstemmed | The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions |
title_short | The Human Antimicrobial Peptides Dermcidin and LL-37 Show Novel Distinct Pathways in Membrane Interactions |
title_sort | human antimicrobial peptides dermcidin and ll-37 show novel distinct pathways in membrane interactions |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5681987/ https://www.ncbi.nlm.nih.gov/pubmed/29164103 http://dx.doi.org/10.3389/fchem.2017.00086 |
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