8QEY

Structure of human Asc1/CD98hc heteromeric amino acid transporter

8QEY の概要

• エントリーDOI: 10.2210/pdb8qey/pdb
• EMDBエントリー: 18379
• 分子名称: 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)
• 機能のキーワード: heteromeric amino acid transporter transporter apc transporter, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 127780.06

構造登録者

Martinez-Molledo, M.,Rullo-Tubau, J.,Errasti-Murugarren, E.,Palacin, M.,Llorca, O. (登録日: 2023-09-01, 公開日: 2024-04-10, 最終更新日: 2025-07-09)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (4 Å)