Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41

The conserved, membrane-proximal external region (MPER) of the human immunodeficiency virus type-1 envelope glycoprotein 41 subunit is required for fusogenic activity. It has been proposed that MPER functions by disrupting the virion membrane. Supporting its critical role in viral entry as a membran...

Descripción completa

Detalles Bibliográficos
Autores: Apellaniz Unzalu, Beatriz, Nir, Shlomo, Nieva Escandón, José Luis
Tipo de recurso: artículo
Fecha de publicación:2009
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/68860
Acceso en línea:http://hdl.handle.net/10810/68860
Access Level:acceso abierto
Palabra clave:fusion peptide
HIV-1
LUVs
MPER
membrane destabilization
lipids
transmembrane domain
pores
all-or-none
graded
requenching
id ES_a56018818d17ea7063edf353c82eda21
oai_identifier_str oai:addi.ehu.eus:10810/68860
network_acronym_str ES
network_name_str España
repository_id_str
spelling Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41Apellaniz Unzalu, BeatrizNir, ShlomoNieva Escandón, José Luisfusion peptideHIV-1LUVsMPERmembrane destabilizationlipidstransmembrane domainporesall-or-nonegradedrequenchingThe conserved, membrane-proximal external region (MPER) of the human immunodeficiency virus type-1 envelope glycoprotein 41 subunit is required for fusogenic activity. It has been proposed that MPER functions by disrupting the virion membrane. Supporting its critical role in viral entry as a membranebound entity, MPER constitutes the target for broadly neutralizing antibodies that have evolved mechanisms to recognize membrane-inserted epitopes. We have analyzed here the molecular mechanisms of membrane permeabilization induced by N-preTM and PreTM-C, two peptides derived from MPERsequences showing a tendency to associate with the bilayer interface or to transfer into the hydrocarbon core, respectively. Both peptides contained the full epitope sequence recognized by the 4E10 monoclonal antibody (MAb4E10), which was subsequently used to probe peptide accessibility from the water phase. Capacities of N-preTM and PreTM-C for associating with vesicles and inducing their permeabilization were comparable. However, MAb4E10 specifically blocked the permeabilization induced by N-preTM but did not appreciably affect that induced by PreTM-C. Supporting the existence of different membrane-bound lytic structures, N-preTM was running as a monomer on SDS-PAGE and induced the graded release of vesicular contents, whereas PreTM-C migrated on SDS-PAGE as dimers and permeabilized vesicles following an all-or-none mechanism, reminiscent of that underlying melittin-induced membrane lysis. These results support the functional segmentation of gp41 membrane regions into hydrophobic subdomains, which might expose neutralizing epitopes and induce membrane-disrupting effects following distinct patterns during the fusion cascade.This study was supported by Spanish MICINN(BIO2008-00772) and University of the BasqueCountry (GIU 06/42 and DIPE08/12). B.A.was a recipient of a predoctoral fellowship of the Spanish MICINN.ACS Publications202420242009info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/68860reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoInglésinfo:eu-repo/grantAgreement/MICINN/BIO2008-00772/https://pubs.acs.org/doi/10.1021/bi900504tinfo:eu-repo/semantics/openAccess© 2009 American Chemical Societyoai:addi.ehu.eus:10810/688602026-06-18T09:23:17Z
dc.title.none.fl_str_mv Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41
title Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41
spellingShingle Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41
Apellaniz Unzalu, Beatriz
fusion peptide
HIV-1
LUVs
MPER
membrane destabilization
lipids
transmembrane domain
pores
all-or-none
graded
requenching
title_short Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41
title_full Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41
title_fullStr Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41
title_full_unstemmed Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41
title_sort Distinct mechanisms of lipid bilayer perturbation induced by peptides derived from the membrane-proximal external region of HIV-1 gp41
dc.creator.none.fl_str_mv Apellaniz Unzalu, Beatriz
Nir, Shlomo
Nieva Escandón, José Luis
author Apellaniz Unzalu, Beatriz
author_facet Apellaniz Unzalu, Beatriz
Nir, Shlomo
Nieva Escandón, José Luis
author_role author
author2 Nir, Shlomo
Nieva Escandón, José Luis
author2_role author
author
dc.subject.none.fl_str_mv fusion peptide
HIV-1
LUVs
MPER
membrane destabilization
lipids
transmembrane domain
pores
all-or-none
graded
requenching
topic fusion peptide
HIV-1
LUVs
MPER
membrane destabilization
lipids
transmembrane domain
pores
all-or-none
graded
requenching
description The conserved, membrane-proximal external region (MPER) of the human immunodeficiency virus type-1 envelope glycoprotein 41 subunit is required for fusogenic activity. It has been proposed that MPER functions by disrupting the virion membrane. Supporting its critical role in viral entry as a membranebound entity, MPER constitutes the target for broadly neutralizing antibodies that have evolved mechanisms to recognize membrane-inserted epitopes. We have analyzed here the molecular mechanisms of membrane permeabilization induced by N-preTM and PreTM-C, two peptides derived from MPERsequences showing a tendency to associate with the bilayer interface or to transfer into the hydrocarbon core, respectively. Both peptides contained the full epitope sequence recognized by the 4E10 monoclonal antibody (MAb4E10), which was subsequently used to probe peptide accessibility from the water phase. Capacities of N-preTM and PreTM-C for associating with vesicles and inducing their permeabilization were comparable. However, MAb4E10 specifically blocked the permeabilization induced by N-preTM but did not appreciably affect that induced by PreTM-C. Supporting the existence of different membrane-bound lytic structures, N-preTM was running as a monomer on SDS-PAGE and induced the graded release of vesicular contents, whereas PreTM-C migrated on SDS-PAGE as dimers and permeabilized vesicles following an all-or-none mechanism, reminiscent of that underlying melittin-induced membrane lysis. These results support the functional segmentation of gp41 membrane regions into hydrophobic subdomains, which might expose neutralizing epitopes and induce membrane-disrupting effects following distinct patterns during the fusion cascade.
publishDate 2009
dc.date.none.fl_str_mv 2009
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/68860
url http://hdl.handle.net/10810/68860
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/MICINN/BIO2008-00772/
https://pubs.acs.org/doi/10.1021/bi900504t
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
© 2009 American Chemical Society
eu_rights_str_mv openAccess
rights_invalid_str_mv © 2009 American Chemical Society
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv ACS Publications
publisher.none.fl_str_mv ACS Publications
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869415610121715712
score 15,811543

Similares en LA Referencia