Structural remodeling and oligomerization of human cathelicidin on membranes suggest fibril-like structures as active species
dc.contributor.author | Sancho Vaello, Enea | |
dc.contributor.author | François, Patrice | |
dc.contributor.author | Bonetti, Eve-Julie | |
dc.contributor.author | Lilie, Hauke | |
dc.contributor.author | Finger, Sebastian | |
dc.contributor.author | Gil-Ortiz, Fernando | |
dc.contributor.author | Gil-Carton, David | |
dc.contributor.author | Zeth, Kornelius | |
dc.date.accessioned | 2018-04-23T14:33:16Z | |
dc.date.available | 2018-04-23T14:33:16Z | |
dc.date.issued | 2017-11-13 | |
dc.identifier.citation | Scientific Reports 7 : (2017) // Article ID 15371 | es_ES |
dc.identifier.issn | 2045-2322 | |
dc.identifier.uri | http://hdl.handle.net/10810/26554 | |
dc.description.abstract | Antimicrobial peptides as part of the mammalian innate immune system target and remove major bacterial pathogens, often through irreversible damage of their cellular membranes. To explore the mechanism by which the important cathelicidin peptide LL-37 of the human innate immune system interacts with membranes, we performed biochemical, biophysical and structural studies. The crystal structure of LL-37 displays dimers of anti-parallel helices and the formation of amphipathic surfaces. Peptide-detergent interactions introduce remodeling of this structure after occupation of defined hydrophobic sites at the dimer interface. Furthermore, hydrophobic nests are shaped between dimer structures providing another scaffold enclosing detergents. Both scaffolds underline the potential of LL-37 to form defined peptide-lipid complexes in vivo. After adopting the activated peptide conformation LL-37 can polymerize and selectively extract bacterial lipids whereby the membrane is destabilized. The supramolecular fibril-like architectures formed in crystals can be reproduced in a peptide-lipid system after nanogold-labelled LL-37 interacted with lipid vesicles as followed by electron microscopy. We suggest that these supramolecular structures represent the LL-37-membrane active state. Collectively, our study provides new insights into the fascinating plasticity of LL-37 demonstrated at atomic resolution and opens the venue for LL-37-based molecules as novel antibiotics. | es_ES |
dc.description.sponsorship | We would like to thank Sandra Delgado for the technical help in the preparation of the cryoEM vitrified grids and Dr. Isabel Uson and Dr. Ivan De Marino for the Arcimboldo software and valuable help. Funding was provided by the Unidad de Biofisica and the IKERBASQUE and MINECO science foundations. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing | es_ES |
dc.relation | info:eu-repo/grantAgreement/MINECO | es_ES |
dc.rights | info:eu-repo/semantics/openAccess | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/es/ | * |
dc.subject | cationic antimicrobial peptides | es_ES |
dc.subject | host-defense | es_ES |
dc.subject | ll-37 | es_ES |
dc.subject | refinement | es_ES |
dc.subject | pore | es_ES |
dc.subject | antibacterial | es_ES |
dc.subject | arcimboldo | es_ES |
dc.subject | resolution | es_ES |
dc.subject | secondary | es_ES |
dc.subject | micelles | es_ES |
dc.title | Structural remodeling and oligomerization of human cathelicidin on membranes suggest fibril-like structures as active species | es_ES |
dc.type | info:eu-repo/semantics/article | es_ES |
dc.rights.holder | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Cre- ative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not per- mitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ | es_ES |
dc.rights.holder | Atribución 3.0 España | * |
dc.relation.publisherversion | https://www.nature.com/articles/s41598-017-14206-1 | es_ES |
dc.identifier.doi | 10.1038/s41598-017-14206-1 | |
dc.departamentoes | Bioquímica y biología molecular | es_ES |
dc.departamentoeu | Biokimika eta biologia molekularra | es_ES |
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