2026-04-14T02:23:34Zhttps://recercat.cat/oai/request

oai:recercat.cat:2117/4117722026-01-21T06:36:11Zcom_2072_1033col_2072_452950

00925njm 22002777a 4500 dc Puch Giner, Ignasi author Arias, Ángela author Saen-oon, Suwipa author Artuch, Rafael author Guallar, Víctor author 2024-04-06 Recent cryoEM studies elucidated details of the structural basis for the substrate selectivity and translocation of heteromeric amino acid transporters. However, Asc1/CD98hc is the only neutral heteromeric amino acid transporter that can function through facilitated diffusion, and the only one that efficiently transports glycine and D-serine, and thus has a regulatory role in the central nervous system. Here we use cryoEM, ligand-binding simulations, mutagenesis, transport assays, and molecular dynamics to define human Asc1/CD98hc determinants for substrate specificity and gain insights into the mechanisms that govern substrate translocation by exchange and facilitated diffusion. The cryoEM structure of Asc1/CD98hc is determined at 3.4–3.8¿Å resolution, revealing an inward-facing semi-occluded conformation. We find that Ser 246 and Tyr 333 are essential for Asc1/CD98hc substrate selectivity and for the exchange and facilitated diffusion modes of transport. Taken together, these results reveal the structural bases for ligand binding and transport features specific to human Asc1. Postprint (published version) Àrees temàtiques de la UPC::Física Membrane proteins Cryoelectron microscopy Membrane proteins Proteïnes de membrana Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter