Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)

Detalhes bibliográficos
Autor(a) principal: Domingues, Marco M.
Data de Publicação: 2009
Outros Autores: Lopes, Sílvia C. D. N., Santos, Nuno C., Quintas, Alexandre, Castanho, Miguel A. R. B.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/7261
Resumo: © 2009 by the Biophysical Society
id RCAP_0f059cb951f9c970ed3dfdf9dd8d1cc2
oai_identifier_str oai:repositorio.ul.pt:10451/7261
network_acronym_str RCAP
network_name_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository_id_str 7160
spelling Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)© 2009 by the Biophysical SocietySeptic or endotoxic shock is a common cause of death in hospital intensive care units. In the last decade numerous antimicrobial peptides and proteins have been tested in the search for an efficient drug to treat this lethal disease. Now in phase III clinical trials, rBPI21, a recombinant N-terminal fragment of the bactericidal/permeability-increasing protein (BPI), is a promising drug to reduce lesions caused by meningococcal sepsis. We correlated structural and stability data with functional information of rBPI21 bound to both model systems of eukaryotic and bacterial membranes. On interaction with membranes, rBPI21 loses its conformational stability, as studied by circular dichroism. This interaction of rBPI21 at membrane level was higher in the presence of negatively charged phospholipid relatively to neutral ones, with higher partition coefficients (Kp), suggesting a preference for bacterial membranes over mammalian membranes. rBPI21 binding to membranes is reinforced when its disulfide bond is broken due to conformational changes of the protein. This interaction is followed by liposome aggregation due to unfolding, which ensures protein aggregation, and interfacial localization of rBPI21 in membranes, as studied by extensive quenching by acrylamide and 5-deoxylstearic acid and not by 16-deoxylstearic acid. An uncommon model of the selectivity and mechanism of action is proposed, where membrane induces unfolding of the antimicrobial protein, rBPI21. The unfolding ensures protein aggregation, established by protein-protein interaction at membrane surface or between adjacent membranes covered by the unfolded protein. This protein aggregation step may lead to membrane perturbation.M.M.D. acknowledges Fundação para a Ciência e a Tecnologia do Ministério da Ciência, Tecnologia e Ensino Superior (Portugal) for fellowship SFRH/BD/41750/2007Biophysical SocietyRepositório da Universidade de LisboaDomingues, Marco M.Lopes, Sílvia C. D. N.Santos, Nuno C.Quintas, AlexandreCastanho, Miguel A. R. B.2012-11-21T15:16:36Z20092009-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/7261engBiophysical Journal 96(3) 987–996, February 20090006-3495hhtp://dx.doi.org/10.1016/j.bpj.2008.10.044info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:50:19Zoai:repositorio.ul.pt:10451/7261Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:32:07.518189Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)
title Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)
spellingShingle Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)
Domingues, Marco M.
title_short Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)
title_full Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)
title_fullStr Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)
title_full_unstemmed Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)
title_sort Fold-unfold transitions in the selectivity and mechanism of action of the N-terminal fragment of the bactericidal/permeability-increasing protein (rBPI21)
author Domingues, Marco M.
author_facet Domingues, Marco M.
Lopes, Sílvia C. D. N.
Santos, Nuno C.
Quintas, Alexandre
Castanho, Miguel A. R. B.
author_role author
author2 Lopes, Sílvia C. D. N.
Santos, Nuno C.
Quintas, Alexandre
Castanho, Miguel A. R. B.
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Domingues, Marco M.
Lopes, Sílvia C. D. N.
Santos, Nuno C.
Quintas, Alexandre
Castanho, Miguel A. R. B.
description © 2009 by the Biophysical Society
publishDate 2009
dc.date.none.fl_str_mv 2009
2009-01-01T00:00:00Z
2012-11-21T15:16:36Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/7261
url http://hdl.handle.net/10451/7261
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Biophysical Journal 96(3) 987–996, February 2009
0006-3495
hhtp://dx.doi.org/10.1016/j.bpj.2008.10.044
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Biophysical Society
publisher.none.fl_str_mv Biophysical Society
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv
_version_ 1799134212175953920

Registros relacionados