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-Structure paper
タイトル | Structure and mechanisms of transport of human Asc1/CD98hc amino acid transporter. |
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ジャーナル・号・ページ | Nat Commun, Vol. 15, Issue 1, Page 2986, Year 2024 |
掲載日 | 2024年4月6日 |
著者 | Josep Rullo-Tubau / Maria Martinez-Molledo / Paola Bartoccioni / Ignasi Puch-Giner / Ángela Arias / Suwipa Saen-Oon / Camille Stephan-Otto Attolini / Rafael Artuch / Lucía Díaz / Víctor Guallar / Ekaitz Errasti-Murugarren / Manuel Palacín / Oscar Llorca / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:38582862 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.0 Å |
構造データ | EMDB-18379, PDB-8qey: |
化合物 | ChemComp-AJP: ChemComp-NAG: |
由来 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / Heteromeric amino acid transporter Transporter APC transporter |