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-Structure paper
タイトル | A one-gate elevator mechanism for the human neutral amino acid transporter ASCT2. |
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ジャーナル・号・ページ | Nat Commun, Vol. 10, Issue 1, Page 3427, Year 2019 |
掲載日 | 2019年7月31日 |
著者 | Alisa A Garaeva / Albert Guskov / Dirk J Slotboom / Cristina Paulino / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:31366933 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.61 - 6.98 Å |
構造データ | EMDB-10016, PDB-6rvx: EMDB-10017: EMDB-10018, PDB-6rvy: |
由来 |
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キーワード | MEMBRANE PROTEIN / solute carrier family 1 (SLC1A) one-gate elevator mechanism neutral amino acid exchange membrane protein cryo-EM / solute carrier family 1 (SLC1A) one-gate elevator mechanism neutral amino acid exchange membrane proteins cryo-EM |