Crystal structure of c5321

Background: Increasing rates of antimicrobial resistance among uropathogens led, among other efforts, to the application of subtractive reverse vaccinology for the identification of antigens present in extraintestinal pathogenic E. coli (ExPEC) strains but absent or variable in non-pathogenic strain...

Descripción completa

Detalles Bibliográficos
Autores: Urosev, Dunja, Ferrer-Navarro, Mario|||0000-0001-9990-914X, Pastorello, Ilaria, Cartocci, Elena, Costenaro, Lionel, Zhulenkovs, Dmitrijs, Maréchal, Jean-Didier|||0000-0002-8344-9043, Leonchiks, Ainars, Reverter Cendrós, David|||0000-0002-5347-0992, Serino, Laura, Soriani, Marco, Daura i Ribera, Xavier|||0000-0001-9235-6730
Tipo de recurso: artículo
Fecha de publicación:2013
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:125687
Acceso en línea:https://ddd.uab.cat/record/125687
https://dx.doi.org/urn:doi:10.1186/1472-6807-13-19
Access Level:acceso abierto
Palabra clave:C5321
Sel1-like repeat
Crystal structure
Super-helical fold
Antigen
Uropathogenic Escherichia coli
id ES_d85a56e1faded47e63cd68b616ffdb0b
oai_identifier_str oai:ddd.uab.cat:125687
network_acronym_str ES
network_name_str España
repository_id_str
spelling Crystal structure of c5321a protective antigen present in uropathogenic Escherichia coli strains displaying an SLR foldUrosev, DunjaFerrer-Navarro, Mario|||0000-0001-9990-914XPastorello, IlariaCartocci, ElenaCostenaro, LionelZhulenkovs, DmitrijsMaréchal, Jean-Didier|||0000-0002-8344-9043Leonchiks, AinarsReverter Cendrós, David|||0000-0002-5347-0992Serino, LauraSoriani, MarcoDaura i Ribera, Xavier|||0000-0001-9235-6730C5321Sel1-like repeatCrystal structureSuper-helical foldAntigenUropathogenic Escherichia coliBackground: Increasing rates of antimicrobial resistance among uropathogens led, among other efforts, to the application of subtractive reverse vaccinology for the identification of antigens present in extraintestinal pathogenic E. coli (ExPEC) strains but absent or variable in non-pathogenic strains, in a quest for a broadly protective Escherichia coli vaccine. The protein coded by locus c5321 from CFT073 E. coli was identified as one of nine potential vaccine candidates against ExPEC and was able to confer protection with an efficacy of 33% in a mouse model of sepsis. c5321 (known also as EsiB) lacks functional annotation and structurally belongs to the Sel1-like repeat (SLR) family. Herein, as part of the general characterization of this potential antigen, we have focused on its structural properties. Results: We report the 1.74 Å-resolution crystal structure of c5321 from CFT073 E. coli determined by Se-Met SAD phasing. The structure is composed of 11 SLR units in a topological organisation that highly resembles that found in HcpC from Helicobacter pylori, with the main difference residing in how the super-helical fold is stabilised. The stabilising effect of disulfide bridges in HcpC is replaced in c5321 by a strengthening of the inter-repeat hydrophobic core. A metal-ion binding site, uncharacteristic of SLR proteins, is detected between SLR units 3 and 4 in the region of the inter-repeat hydrophobic core. Crystal contacts are observed between the C-terminal tail of one molecule and the C-terminal amphipathic groove of a neighbouring one, resembling interactions between ligand and proteins containing tetratricopeptide-like repeats. Conclusions: The structure of antigen c5321 presents a mode of stabilization of the SLR fold different from that observed in close homologs of known structure. The location of the metal-ion binding site and the observed crystalcontacts suggest a potential role in regulation of conformational flexibility and interaction with yet unidentified target proteins, respectively. These findings open new perspectives in both antigen design and for the identification of a functional role for this protective antigen. 22013-01-0120132013-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/125687https://dx.doi.org/urn:doi:10.1186/1472-6807-13-19reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengEuropean Commission https://doi.org/10.13039/501100000780 037325open accesshttp://purl.org/coar/access_right/c_abf2Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1256872026-06-06T12:50:31Z
dc.title.none.fl_str_mv Crystal structure of c5321
a protective antigen present in uropathogenic Escherichia coli strains displaying an SLR fold
title Crystal structure of c5321
spellingShingle Crystal structure of c5321
Urosev, Dunja
C5321
Sel1-like repeat
Crystal structure
Super-helical fold
Antigen
Uropathogenic Escherichia coli
title_short Crystal structure of c5321
title_full Crystal structure of c5321
title_fullStr Crystal structure of c5321
title_full_unstemmed Crystal structure of c5321
title_sort Crystal structure of c5321
dc.creator.none.fl_str_mv Urosev, Dunja
Ferrer-Navarro, Mario|||0000-0001-9990-914X
Pastorello, Ilaria
Cartocci, Elena
Costenaro, Lionel
Zhulenkovs, Dmitrijs
Maréchal, Jean-Didier|||0000-0002-8344-9043
Leonchiks, Ainars
Reverter Cendrós, David|||0000-0002-5347-0992
Serino, Laura
Soriani, Marco
Daura i Ribera, Xavier|||0000-0001-9235-6730
author Urosev, Dunja
author_facet Urosev, Dunja
Ferrer-Navarro, Mario|||0000-0001-9990-914X
Pastorello, Ilaria
Cartocci, Elena
Costenaro, Lionel
Zhulenkovs, Dmitrijs
Maréchal, Jean-Didier|||0000-0002-8344-9043
Leonchiks, Ainars
Reverter Cendrós, David|||0000-0002-5347-0992
Serino, Laura
Soriani, Marco
Daura i Ribera, Xavier|||0000-0001-9235-6730
author_role author
author2 Ferrer-Navarro, Mario|||0000-0001-9990-914X
Pastorello, Ilaria
Cartocci, Elena
Costenaro, Lionel
Zhulenkovs, Dmitrijs
Maréchal, Jean-Didier|||0000-0002-8344-9043
Leonchiks, Ainars
Reverter Cendrós, David|||0000-0002-5347-0992
Serino, Laura
Soriani, Marco
Daura i Ribera, Xavier|||0000-0001-9235-6730
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv C5321
Sel1-like repeat
Crystal structure
Super-helical fold
Antigen
Uropathogenic Escherichia coli
topic C5321
Sel1-like repeat
Crystal structure
Super-helical fold
Antigen
Uropathogenic Escherichia coli
description Background: Increasing rates of antimicrobial resistance among uropathogens led, among other efforts, to the application of subtractive reverse vaccinology for the identification of antigens present in extraintestinal pathogenic E. coli (ExPEC) strains but absent or variable in non-pathogenic strains, in a quest for a broadly protective Escherichia coli vaccine. The protein coded by locus c5321 from CFT073 E. coli was identified as one of nine potential vaccine candidates against ExPEC and was able to confer protection with an efficacy of 33% in a mouse model of sepsis. c5321 (known also as EsiB) lacks functional annotation and structurally belongs to the Sel1-like repeat (SLR) family. Herein, as part of the general characterization of this potential antigen, we have focused on its structural properties. Results: We report the 1.74 Å-resolution crystal structure of c5321 from CFT073 E. coli determined by Se-Met SAD phasing. The structure is composed of 11 SLR units in a topological organisation that highly resembles that found in HcpC from Helicobacter pylori, with the main difference residing in how the super-helical fold is stabilised. The stabilising effect of disulfide bridges in HcpC is replaced in c5321 by a strengthening of the inter-repeat hydrophobic core. A metal-ion binding site, uncharacteristic of SLR proteins, is detected between SLR units 3 and 4 in the region of the inter-repeat hydrophobic core. Crystal contacts are observed between the C-terminal tail of one molecule and the C-terminal amphipathic groove of a neighbouring one, resembling interactions between ligand and proteins containing tetratricopeptide-like repeats. Conclusions: The structure of antigen c5321 presents a mode of stabilization of the SLR fold different from that observed in close homologs of known structure. The location of the metal-ion binding site and the observed crystalcontacts suggest a potential role in regulation of conformational flexibility and interaction with yet unidentified target proteins, respectively. These findings open new perspectives in both antigen design and for the identification of a functional role for this protective antigen.
publishDate 2013
dc.date.none.fl_str_mv 2
2013-01-01
2013
2013-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/125687
https://dx.doi.org/urn:doi:10.1186/1472-6807-13-19
url https://ddd.uab.cat/record/125687
https://dx.doi.org/urn:doi:10.1186/1472-6807-13-19
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.relation.none.fl_str_mv European Commission https://doi.org/10.13039/501100000780 037325
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869421117656006656
score 15,301603

Similares en LA Referencia