Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes

Autores
Heinrich, Frank; Salyapongse, Aria; Kumagai, Akari; Dupuy, Fernando Gabriel; Shukla, Karpur; Penk, Anja; Huster, Daniel; Ernst, Robert K.; Pavlova, Anna; Gumbart, James C.; Deslouches, Berthony; Di, Y. Peter; Tristram-Nagle, Stephanie
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d-enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.
Fil: Heinrich, Frank. University of Carnegie Mellon; Estados Unidos
Fil: Salyapongse, Aria. University of Carnegie Mellon; Estados Unidos
Fil: Kumagai, Akari. University of Carnegie Mellon; Estados Unidos
Fil: Dupuy, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Shukla, Karpur. University of Carnegie Mellon; Estados Unidos
Fil: Penk, Anja. Universitat Leipzig; Alemania
Fil: Huster, Daniel. Universitat Leipzig; Alemania
Fil: Ernst, Robert K.. University of Maryland; Estados Unidos
Fil: Pavlova, Anna. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados Unidos
Fil: Gumbart, James C.. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados Unidos
Fil: Deslouches, Berthony. University of Pittsburgh; Estados Unidos
Fil: Di, Y. Peter. University of Pittsburgh; Estados Unidos
Fil: Tristram-Nagle, Stephanie. University of Carnegie Mellon; Estados Unidos
Materia
DRUG DESIGN
ENGINEERED CATIONIC ANTIMICROBIAL PEPTIDES
MEMBRANES
NEUTRON REFLECTIVITY
PROTEIN–LIPID INTERACTIONS
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/184335
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/184335
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model MembranesHeinrich, FrankSalyapongse, AriaKumagai, AkariDupuy, Fernando GabrielShukla, KarpurPenk, AnjaHuster, DanielErnst, Robert K.Pavlova, AnnaGumbart, James C.Deslouches, BerthonyDi, Y. PeterTristram-Nagle, StephanieDRUG DESIGNENGINEERED CATIONIC ANTIMICROBIAL PEPTIDESMEMBRANESNEUTRON REFLECTIVITYPROTEIN–LIPID INTERACTIONShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d-enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.Fil: Heinrich, Frank. University of Carnegie Mellon; Estados UnidosFil: Salyapongse, Aria. University of Carnegie Mellon; Estados UnidosFil: Kumagai, Akari. University of Carnegie Mellon; Estados UnidosFil: Dupuy, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; ArgentinaFil: Shukla, Karpur. University of Carnegie Mellon; Estados UnidosFil: Penk, Anja. Universitat Leipzig; AlemaniaFil: Huster, Daniel. Universitat Leipzig; AlemaniaFil: Ernst, Robert K.. University of Maryland; Estados UnidosFil: Pavlova, Anna. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados UnidosFil: Gumbart, James C.. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados UnidosFil: Deslouches, Berthony. University of Pittsburgh; Estados UnidosFil: Di, Y. Peter. University of Pittsburgh; Estados UnidosFil: Tristram-Nagle, Stephanie. University of Carnegie Mellon; Estados UnidosWiley VCH Verlag2020-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/184335Heinrich, Frank; Salyapongse, Aria; Kumagai, Akari; Dupuy, Fernando Gabriel; Shukla, Karpur; et al.; Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes; Wiley VCH Verlag; Chemistry- A European Journal; 26; 28; 5-2020; 6247-62560947-6539CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.202000212info:eu-repo/semantics/altIdentifier/doi/10.1002/chem.202000212info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T12:10:47Zoai:ri.conicet.gov.ar:11336/184335instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-22 12:10:47.437CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes
title Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes
spellingShingle Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes
Heinrich, Frank
DRUG DESIGN
ENGINEERED CATIONIC ANTIMICROBIAL PEPTIDES
MEMBRANES
NEUTRON REFLECTIVITY
PROTEIN–LIPID INTERACTIONS
title_short Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes
title_full Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes
title_fullStr Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes
title_full_unstemmed Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes
title_sort Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes
dc.creator.none.fl_str_mv Heinrich, Frank
Salyapongse, Aria
Kumagai, Akari
Dupuy, Fernando Gabriel
Shukla, Karpur
Penk, Anja
Huster, Daniel
Ernst, Robert K.
Pavlova, Anna
Gumbart, James C.
Deslouches, Berthony
Di, Y. Peter
Tristram-Nagle, Stephanie
author Heinrich, Frank
author_facet Heinrich, Frank
Salyapongse, Aria
Kumagai, Akari
Dupuy, Fernando Gabriel
Shukla, Karpur
Penk, Anja
Huster, Daniel
Ernst, Robert K.
Pavlova, Anna
Gumbart, James C.
Deslouches, Berthony
Di, Y. Peter
Tristram-Nagle, Stephanie
author_role author
author2 Salyapongse, Aria
Kumagai, Akari
Dupuy, Fernando Gabriel
Shukla, Karpur
Penk, Anja
Huster, Daniel
Ernst, Robert K.
Pavlova, Anna
Gumbart, James C.
Deslouches, Berthony
Di, Y. Peter
Tristram-Nagle, Stephanie
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv DRUG DESIGN
ENGINEERED CATIONIC ANTIMICROBIAL PEPTIDES
MEMBRANES
NEUTRON REFLECTIVITY
PROTEIN–LIPID INTERACTIONS
topic DRUG DESIGN
ENGINEERED CATIONIC ANTIMICROBIAL PEPTIDES
MEMBRANES
NEUTRON REFLECTIVITY
PROTEIN–LIPID INTERACTIONS
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d-enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.
Fil: Heinrich, Frank. University of Carnegie Mellon; Estados Unidos
Fil: Salyapongse, Aria. University of Carnegie Mellon; Estados Unidos
Fil: Kumagai, Akari. University of Carnegie Mellon; Estados Unidos
Fil: Dupuy, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Fil: Shukla, Karpur. University of Carnegie Mellon; Estados Unidos
Fil: Penk, Anja. Universitat Leipzig; Alemania
Fil: Huster, Daniel. Universitat Leipzig; Alemania
Fil: Ernst, Robert K.. University of Maryland; Estados Unidos
Fil: Pavlova, Anna. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados Unidos
Fil: Gumbart, James C.. Georgia Institute Of Techology. School Of Chemical & Biomolecular Engineering; Estados Unidos
Fil: Deslouches, Berthony. University of Pittsburgh; Estados Unidos
Fil: Di, Y. Peter. University of Pittsburgh; Estados Unidos
Fil: Tristram-Nagle, Stephanie. University of Carnegie Mellon; Estados Unidos
description In the quest for new antibiotics, two novel engineered cationic antimicrobial peptides (eCAPs) have been rationally designed. WLBU2 and D8 (all 8 valines are the d-enantiomer) efficiently kill both Gram-negative and -positive bacteria, but WLBU2 is toxic and D8 nontoxic to eukaryotic cells. We explore protein secondary structure, location of peptides in six lipid model membranes, changes in membrane structure and pore evidence. We suggest that protein secondary structure is not a critical determinant of bactericidal activity, but that membrane thinning and dual location of WLBU2 and D8 in the membrane headgroup and hydrocarbon region may be important. While neither peptide thins the Gram-negative lipopolysaccharide outer membrane model, both locate deep into its hydrocarbon region where they are primed for self-promoted uptake into the periplasm. The partially α-helical secondary structure of WLBU2 in a red blood cell (RBC) membrane model containing 50 % cholesterol, could play a role in destabilizing this RBC membrane model causing pore formation that is not observed with the D8 random coil, which correlates with RBC hemolysis caused by WLBU2 but not by D8.
publishDate 2020
dc.date.none.fl_str_mv 2020-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/184335
Heinrich, Frank; Salyapongse, Aria; Kumagai, Akari; Dupuy, Fernando Gabriel; Shukla, Karpur; et al.; Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes; Wiley VCH Verlag; Chemistry- A European Journal; 26; 28; 5-2020; 6247-6256
0947-6539
CONICET Digital
CONICET
url http://hdl.handle.net/11336/184335
identifier_str_mv Heinrich, Frank; Salyapongse, Aria; Kumagai, Akari; Dupuy, Fernando Gabriel; Shukla, Karpur; et al.; Synergistic Biophysical Techniques Reveal Structural Mechanisms of Engineered Cationic Antimicrobial Peptides in Lipid Model Membranes; Wiley VCH Verlag; Chemistry- A European Journal; 26; 28; 5-2020; 6247-6256
0947-6539
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.202000212
info:eu-repo/semantics/altIdentifier/doi/10.1002/chem.202000212
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 12.982451

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