7P9V
Cryo EM structure of System XC-
Summary for 7P9V
| Entry DOI | 10.2210/pdb7p9v/pdb |
| Related | 7P9U |
| EMDB information | 13266 13267 |
| Descriptor | 4F2 cell-surface antigen heavy chain, Cystine/glutamate transporter, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose (3 entities in total) |
| Functional Keywords | transporter glutamate cystine, membrane protein |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 2 |
| Total formula weight | 127326.08 |
| Authors | Parker, J.L.,Deme, J.C.,Lea, S.M.,Newstead, S. (deposition date: 2021-07-28, release date: 2021-11-17, Last modification date: 2024-11-13) |
| Primary citation | 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 Cited by 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: 34880232DOI: 10.1038/s41467-021-27414-1 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.4 Å) |
Structure validation
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