L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction

© The Author(s) 2019.

Detalles Bibliográficos
Autores: Errasti-Murugarren, Ekaitz, Fort, Joana, Bartoccioni, Paola, Díaz Bueno, Lucía, Pardon, Els, Carpena, Xavi, Espino-Guarch, Meritxell, Zorzano, Antonio, Ziegler, Christine, Steyaert, Jan, Fernández-Recio, Juan, Fita, Ignacio, Palacín, Manuel
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2019
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/201579
Acceso en línea:http://hdl.handle.net/10261/201579
Access Level:acceso abierto
Palabra clave:Membrane proteins
X-ray crystallography
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spelling L amino acid transporter structure and molecular bases for the asymmetry of substrate interactionErrasti-Murugarren, EkaitzFort, JoanaBartoccioni, PaolaDíaz Bueno, LucíaPardon, ElsCarpena, XaviEspino-Guarch, MeritxellZorzano, AntonioZiegler, ChristineSteyaert, JanFernández-Recio, JuanFita, IgnacioPalacín, ManuelMembrane proteinsX-ray crystallography© The Author(s) 2019.L-amino acid transporters (LATs) play key roles in human physiology and are implicated in several human pathologies. LATs are asymmetric amino acid exchangers where the low apparent affinity cytoplasmic side controls the exchange of substrates with high apparent affinity on the extracellular side. Here, we report the crystal structures of an LAT, the bacterial alanine-serine-cysteine exchanger (BasC), in a non-occluded inward-facing conformation in both apo and substrate-bound states. We crystallized BasC in complex with a nanobody, which blocks the transporter from the intracellular side, thus unveiling the sidedness of the substrate interaction of BasC. Two conserved residues in human LATs, Tyr 236 and Lys 154, are located in equivalent positions to the Na1 and Na2 sites of sodiumdependent APC superfamily transporters. Functional studies and molecular dynamics (MD) calculations reveal that these residues are key for the asymmetric substrate interaction of BasC and in the homologous human transporter Asc-1.This work was funded by the Spanish Ministry of Science and Innovation (grant SAF2015-64869-R-FEDER), the Fundació la Marató TV3 (20132330), Research Contract with SIDRA Medicine (Qatar), CIBERER ACCI 2017-U731, and the Generalitat de Catalunya (grant SGR2009-1355).Springer NatureMinisterio de Economía y Competitividad (España)European CommissionFundació La Marató de TV3Generalitat de CatalunyaConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]2020202020192020info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/201579reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64869-Rhttp://dx.doi.org/10.1038/s41467-019-09837-zSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2015792026-05-22T06:33:51Z
dc.title.none.fl_str_mv L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction
title L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction
spellingShingle L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction
Errasti-Murugarren, Ekaitz
Membrane proteins
X-ray crystallography
title_short L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction
title_full L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction
title_fullStr L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction
title_full_unstemmed L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction
title_sort L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction
dc.creator.none.fl_str_mv Errasti-Murugarren, Ekaitz
Fort, Joana
Bartoccioni, Paola
Díaz Bueno, Lucía
Pardon, Els
Carpena, Xavi
Espino-Guarch, Meritxell
Zorzano, Antonio
Ziegler, Christine
Steyaert, Jan
Fernández-Recio, Juan
Fita, Ignacio
Palacín, Manuel
author Errasti-Murugarren, Ekaitz
author_facet Errasti-Murugarren, Ekaitz
Fort, Joana
Bartoccioni, Paola
Díaz Bueno, Lucía
Pardon, Els
Carpena, Xavi
Espino-Guarch, Meritxell
Zorzano, Antonio
Ziegler, Christine
Steyaert, Jan
Fernández-Recio, Juan
Fita, Ignacio
Palacín, Manuel
author_role author
author2 Fort, Joana
Bartoccioni, Paola
Díaz Bueno, Lucía
Pardon, Els
Carpena, Xavi
Espino-Guarch, Meritxell
Zorzano, Antonio
Ziegler, Christine
Steyaert, Jan
Fernández-Recio, Juan
Fita, Ignacio
Palacín, Manuel
author2_role author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Economía y Competitividad (España)
European Commission
Fundació La Marató de TV3
Generalitat de Catalunya
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Membrane proteins
X-ray crystallography
topic Membrane proteins
X-ray crystallography
description © The Author(s) 2019.
publishDate 2019
dc.date.none.fl_str_mv 2019
2020
2020
2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/201579
url http://hdl.handle.net/10261/201579
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64869-R
http://dx.doi.org/10.1038/s41467-019-09837-z
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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