2026-04-17T05:45:37Zhttps://recercat.cat/oai/request

oai:recercat.cat:10230/441492025-12-12T01:47:47Zcom_2072_6col_2072_452952

00925njm 22002777a 4500 dc Errasti-Murugarren, Ekaitz author Fort, Joana author Bartoccioni, Paola author Díaz, Lucía author Pardon, Els author Carpena, Xavier author Espino Guarch, Meritxell author Zorzano, Antonio author Ziegler, Christine author Steyaert, Jan author Fernández Recio, Juan author Fita, Ignacio author Palacín Mateo, Manuel author 2020-04-02T10:20:31Z 2020-04-02T10:20:31Z 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 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. 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). Membrane proteins X-ray crystallography L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction