7P9U

Cryo EM structure of System XC- in complex with glutamate

7P9U の概要

• エントリーDOI: 10.2210/pdb7p9u/pdb
• EMDBエントリー: 13266
• 分子名称: 4F2 cell-surface antigen heavy chain, Cystine/glutamate transporter, GLUTAMIC ACID (3 entities in total)
• 機能のキーワード: transporter glutamate cystine, 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: 125775.60

構造登録者

Parker, J.L.,Deme, J.C.,Lea, S.M.,Newstead, S. (登録日: 2021-07-28, 公開日: 2021-11-17, 最終更新日: 2022-02-02)

主引用文献

Parker, J.L.,Deme, J.C.,Kolokouris, D.,Kuteyi, G.,Biggin, P.C.,Lea, S.M.,Newstead, S.
Molecular basis for redox control by the human cystine/glutamate antiporter system xc .
Nat Commun, 12:7147-7147, 2021

PubMed Abstract: Cysteine plays an essential role in cellular redox homoeostasis as a key constituent of the tripeptide glutathione (GSH). A rate limiting step in cellular GSH synthesis is the availability of cysteine. However, circulating cysteine exists in the blood as the oxidised di-peptide cystine, requiring specialised transport systems for its import into the cell. System xc is a dedicated cystine transporter, importing cystine in exchange for intracellular glutamate. To counteract elevated levels of reactive oxygen species in cancerous cells system xc is frequently upregulated, making it an attractive target for anticancer therapies. However, the molecular basis for ligand recognition remains elusive, hampering efforts to specifically target this transport system. Here we present the cryo-EM structure of system xc in both the apo and glutamate bound states. Structural comparisons reveal an allosteric mechanism for ligand discrimination, supported by molecular dynamics and cell-based assays, establishing a mechanism for cystine transport in human cells.

PubMed: 34880232
DOI: 10.1038/s41467-021-27414-1

実験手法

ELECTRON MICROSCOPY (3.7 Å)