2026-04-29T00:59:49Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/230932024-11-28T18:24:26Zcom_20.500.12105_2173com_20.500.12105_2051com_20.500.12105_15322col_20.500.12105_19597col_20.500.12105_16962
Repisalud author Rullo-Tubau, Josep author Martinez-Molledo, Maria author Bartoccioni, Paola author Puch-Giner, Ignasi author Arias, Ángela author Saen-Oon, Suwipa author Stephan-Otto Attolini, Camille author Artuch, Rafael author Díaz, Lucía author Guallar, Víctor author Errasti-Murugarren, Ekaitz author Palacín, Manuel author Llorca Blanco, Oscar Antonio funder Fundación La Caixa funder Instituto de Salud Carlos III funder Ministerio de Ciencia, Innovación y Universidades (España) 2024-09-16T08:17:00Z 2024-09-16T08:17:00Z 2024-04-06 Nat Commun . 2024;15(1):2986. https://hdl.handle.net/20.500.12105/23093 38582862 10.1038/s41467-024-47385-3 2041-1723 Nature communications 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 � 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. eng Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter. research article