dc.creator | Zouhir, Samira | |
dc.creator | Bernal Bayard, Joaquín | |
dc.creator | Cordero Alba, Mar | |
dc.creator | Cardenal Muñoz, Elena | |
dc.creator | Guimaraes, Beatriz | |
dc.creator | Lazar, Noureddine | |
dc.creator | Ramos Morales, Francisco | |
dc.creator | Nessler, Sylvie | |
dc.date.accessioned | 2016-02-15T11:15:25Z | |
dc.date.available | 2016-02-15T11:15:25Z | |
dc.date.issued | 2014-11-15 | |
dc.identifier.issn | 0264-6021 | es |
dc.identifier.uri | http://hdl.handle.net/11441/34759 | |
dc.description.abstract | Salmonella infections are a leading cause of bacterial foodborne illness in the United States and the
European Union. Antimicrobial therapy is often administered to treat the infection but increasing isolates
are being detected that demonstrate resistance to multiple antibiotics. Salmonella enterica contains two
virulence related type-III secretion systems (T3SS): one promotes invasion of the intestine and the other
one mediates systemic disease. Both of them secrete the SlrP protein acting as E3 ubiquitin ligase in
human host cells where it targets thioredoxin-1 (Trx1). SlrP belongs to the NEL family of bacterial E3
ubiquitin ligases that have been observed in two distinct autoinhibitory conformations. We solved the 3D
structure of the SlrP/Trx1 complex and determined the Trx1 ubiquitination site. The description of the
substrate-binding mode sheds light on the first step of the activation mechanism of SlrP. Comparison with
the available structural data of other NEL effectors allowed us to gain new insights into their
autoinhibitory mechanism. We propose a molecular mechanism for the regulation of SlrP in which
structural constraints sequestrating the NEL domain would be sequentially released. This work thus
constitutes a new milestone in the understanding of how these T3SS effectors influence pathogen
virulence. It also provides the fundamental basis for future development of new antimicrobials. | es |
dc.description.sponsorship | Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, Spain. Grant P08-CVI-03487 | es |
dc.description.sponsorship | Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund. SAF2010-15015 and SAF2013-46229-R | es |
dc.description.sponsorship | Spanish Ministry of Science and Innovation. Grant FR2009-0103 | es |
dc.description.sponsorship | Programme Picasso-2010 from the Partenariat Hubert Curien | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | Portland Press | es |
dc.relation.ispartof | Biochemical Journal | es |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Salmonella infection | es |
dc.subject | Effector-host protein interaction | es |
dc.subject | Crystal structure | es |
dc.subject | LRR domain | es |
dc.subject | Ubiquitination | es |
dc.subject | Novel bacterial E3 ligase | es |
dc.title | The Structure of the SlrP-hTrx1 Complex Sheds Light on the Autoinhibition Mechanism of the Type-III Secretion System Effectors of the NEL Family | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Genética | es |
dc.relation.publisherversion | http://www.biochemj.org/content/464/1/135 | es |
dc.relation.publisherversion | dx.doi.org/10.1042/BJ20140587 | es |
dc.relation.publisherversion | http://dx.doi.org/10.1042/BJ20140587 | |
dc.identifier.doi | 10.1042/BJ20140587 | |
dc.identifier.idus | https://idus.us.es/xmlui/handle/11441/34759 | |