6RVY

Inward-open structure of the ASCT2 (SLC1A5) mutant C467R in absence of substrate

Summary for 6RVY

• Entry DOI: 10.2210/pdb6rvy/pdb
• Related: 6RVX
• EMDB information: 10016 10017 10018
• Descriptor: Neutral amino acid transporter B(0) (1 entity in total)
• Functional Keywords: solute carrier family 1 (slc1a) one-gate elevator mechanism neutral amino acid exchange membrane proteins cryo-em, membrane protein
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 3
• Total formula weight: 172565.54

Authors

Garaeva, A.A.,Guskov, A.,Slotboom, D.J.,Paulino, C. (deposition date: 2019-06-03, release date: 2019-08-07, Last modification date: 2024-05-22)

Primary citation

Garaeva, A.A.,Guskov, A.,Slotboom, D.J.,Paulino, C.
A one-gate elevator mechanism for the human neutral amino acid transporter ASCT2.
Nat Commun, 10:3427-3427, 2019

PubMed Abstract: The human Alanine Serine Cysteine Transporter 2 (ASCT2) is a neutral amino acid exchanger that belongs to the solute carrier family 1 (SLC1A). SLC1A structures have revealed an elevator-type mechanism, in which the substrate is translocated across the cell membrane by a large displacement of the transport domain, whereas a small movement of hairpin 2 (HP2) gates the extracellular access to the substrate-binding site. However, it has remained unclear how substrate binding and release is gated on the cytoplasmic side. Here, we present an inward-open structure of the human ASCT2, revealing a hitherto elusive SLC1A conformation. Strikingly, the same structural element (HP2) serves as a gate in the inward-facing as in the outward-facing state. The structures reveal that SLC1A transporters work as one-gate elevators. Unassigned densities near the gate and surrounding the scaffold domain, may represent potential allosteric binding sites, which could guide the design of lipidic-inhibitors for anticancer therapy.

PubMed: 31366933
DOI: 10.1038/s41467-019-11363-x

Experimental method

ELECTRON MICROSCOPY (4.13 Å)