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

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dc.contributor.author Errasti-Murugarren, Ekaitz
dc.contributor.author Fort, Joana
dc.contributor.author Bartoccioni, Paola
dc.contributor.author Díaz, Lucía
dc.contributor.author Pardon, Els
dc.contributor.author Carpena, Xavier
dc.contributor.author Espino Guarch, Meritxell
dc.contributor.author Zorzano, Antonio
dc.contributor.author Ziegler, Christine
dc.contributor.author Steyaert, Jan
dc.contributor.author Fernández Recio, Juan
dc.contributor.author Fita, Ignacio
dc.contributor.author Palacín Mateo, Manuel
dc.date.accessioned 2020-04-02T10:20:31Z
dc.date.available 2020-04-02T10:20:31Z
dc.date.issued 2019
dc.identifier.citation Errasti-Murugarren E, Fort J, Bartoccioni P, Díaz L, Pardon E, Carpena X, Espino-Guarch M, Zorzano A, Ziegler C, Steyaert J, Fernández-Recio J, Fita I, Palacín M. L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction. Nat Commun. 2019; 10(1):1807. DOI: 10.1038/s41467-019-09837-z
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/44149
dc.description.abstract 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 sodium-dependent 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.
dc.description.sponsorship 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).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Commun. 2019; 10(1):1807
dc.rights © The Author(s) 2019. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41467-019-09837-z
dc.subject.keyword Membrane proteins
dc.subject.keyword X-ray crystallography
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2015-64869-R
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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