Errasti-Murugarren, Ekaitz and Fort, Joana and Bartoccioni, Paola and Diaz, Lucia and Pardon, Els and Carpena, Xavier and Espino-Guarch, Meritxell and Zorzano, Antonio and Ziegler, Christine and Steyaert, Jan and Fernandez-Recio, Juan and Fita, Ignacio and Palacin, Manuel (2019) L amino acid transporter structure and molecular bases for the asymmetry of substrate interaction. NATURE COMMUNICATIONS, 10: 1807. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LYSINURIC PROTEIN INTOLERANCE; GUI MEMBRANE-BUILDER; MECHANISM; NA+; INHIBITOR; MODEL; SYSTEM; IDENTIFICATION; SIMULATIONS; ACTIVATION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Christine Ziegler |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Apr 2020 08:57 |
| Last Modified: | 15 Apr 2020 08:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27157 |
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