Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Structural basis of the obligatory exchange mode of human neutral amino acid transporter ASCT2.
Journal, issue, pages	Nat Commun, Vol. 15, Issue 1, Page 6570, Year 2024
Publish date	Aug 3, 2024
Authors	Anna M Borowska / Maria Gabriella Chiariello / Alisa A Garaeva / Jan Rheinberger / Siewert J Marrink / Cristina Paulino / Dirk J Slotboom /
PubMed Abstract	ASCT2 is an obligate exchanger of neutral amino acids, contributing to cellular amino acid homeostasis. ASCT2 belongs to the same family (SLC1) as Excitatory Amino Acid Transporters (EAATs) that ...ASCT2 is an obligate exchanger of neutral amino acids, contributing to cellular amino acid homeostasis. ASCT2 belongs to the same family (SLC1) as Excitatory Amino Acid Transporters (EAATs) that concentrate glutamate in the cytosol. The mechanism that makes ASCT2 an exchanger rather than a concentrator remains enigmatic. Here, we employ cryo-electron microscopy and molecular dynamics simulations to elucidate the structural basis of the exchange mechanism of ASCT2. We establish that ASCT2 binds three Na ions per transported substrate and visits a state that likely acts as checkpoint in preventing Na ion leakage, both features shared with EAATs. However, in contrast to EAATs, ASCT2 retains one Na ion even under Na-depleted conditions. We demonstrate that ASCT2 cannot undergo the structural transition in TM7 that is essential for the concentrative transport cycle of EAATs. This structural rigidity and the high-affinity Na binding site effectively confine ASCT2 to an exchange mode.
External links	Nat Commun / PubMed:39095408 / PubMed Central
Methods	EM (single particle)
Resolution	2.6 - 3.0 Å
Structure data	18621 EMDB entry, No image 8qro EMDB-18621, PDB-8qro: ASCT2 trimer in lipid nanodiscs with bound glutamine and Na+ ions in the outward-facing state (OFS) Method: EM (single particle) / Resolution: 2.6 Å 18622 EMDB entry, No image 8qrp EMDB-18622, PDB-8qrp: ASCT2 protomer in lipid nanodiscs with bound glutamine and Na+ ions in the outward-facing state (OFS.1) Method: EM (single particle) / Resolution: 2.7 Å 18623 EMDB entry, No image 8qrq EMDB-18623, PDB-8qrq: ASCT2 protomer in lipid nanodiscs with bound glutamine and Na+ ions in the outward-facing state (OFS.2) Method: EM (single particle) / Resolution: 2.74 Å 18624 EMDB entry, No image 8qrr EMDB-18624, PDB-8qrr: ASCT2 protomer in lipid nanodiscs with bound glutamine and Na+ ions in the outward-facing state (OFS.3) Method: EM (single particle) / Resolution: 2.78 Å 18625 EMDB entry, No image 8qrs EMDB-18625, PDB-8qrs: ASCT2 protomer in lipid nanodiscs with bound glutamine and Na+ ions in the intermediate outward-facing state (iOFS-up) Method: EM (single particle) / Resolution: 2.86 Å 18626 EMDB entry, No image 8qru EMDB-18626, PDB-8qru: ASCT2 protomer in lipid nanodiscs with bound glutamine and Na+ ions in the intermediate outward-facing state (iOFS-down) Method: EM (single particle) / Resolution: 2.9 Å 18627 EMDB entry, No image 8qrv EMDB-18627, PDB-8qrv: ASCT2 protomer in lipid nanodiscs under low Na+ concentration in the outward-facing state (OFS) Method: EM (single particle) / Resolution: 2.9 Å 18628 EMDB entry, No image 8qrw EMDB-18628, PDB-8qrw: ASCT2 protomer in lipid nanodiscs under low Na+ concentration in the intermediate outward-facing state (iOFS-up) Method: EM (single particle) / Resolution: 3.0 Å
Chemicals	ChemComp-NA: Unknown entry ChemComp-GLN: GLUTAMINE
Source	homo sapiens (human)
Keywords	TRANSPORT PROTEIN / neutral amino acid exchanger amino acid transport system elevator transporter glutamine transport