6RVX

Inward-open structure of the ASCT2 (SLC1A5) mutant C467R in presence of TBOA

6RVX の概要

• エントリーDOI: 10.2210/pdb6rvx/pdb
• 関連するPDBエントリー: 6RVY
• EMDBエントリー: 10016 10017 10018
• 分子名称: Neutral amino acid transporter B(0) (1 entity in total)
• 機能のキーワード: solute carrier family 1 (slc1a) one-gate elevator mechanism neutral amino acid exchange membrane protein cryo-em, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 172565.54

構造登録者

Garaeva, A.A.,Guskov, A.,Slotboom, D.J.,Paulino, C. (登録日: 2019-06-03, 公開日: 2019-08-07, 最終更新日: 2024-05-22)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.61 Å)