8QEY

Structure of human Asc1/CD98hc heteromeric amino acid transporter

Summary for 8QEY

• Entry DOI: 10.2210/pdb8qey/pdb
• EMDB information: 18379
• Descriptor: Asc-type amino acid transporter 1, 4F2 cell-surface antigen heavy chain, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (6 entities in total)
• Functional Keywords: heteromeric amino acid transporter transporter apc transporter, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 2
• Total formula weight: 127780.06

Authors

Martinez-Molledo, M.,Rullo-Tubau, J.,Errasti-Murugarren, E.,Palacin, M.,Llorca, O. (deposition date: 2023-09-01, release date: 2024-04-10, Last modification date: 2025-07-09)

Primary citation

Rullo-Tubau, J.,Martinez-Molledo, M.,Bartoccioni, P.,Puch-Giner, I.,Arias, A.,Saen-Oon, S.,Stephan-Otto Attolini, C.,Artuch, R.,Diaz, L.,Guallar, V.,Errasti-Murugarren, E.,Palacin, M.,Llorca, O.
Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter.
Nat Commun, 15:2986-2986, 2024

PubMed Abstract: 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.

PubMed: 38582862
DOI: 10.1038/s41467-024-47385-3

Experimental method

ELECTRON MICROSCOPY (4 Å)