6rvy | pdb_00006rvy
Inward-open structure of the ASCT2 (SLC1A5) mutant C467R in absence of substrate
Structural highlights
Function[AAAT_HUMAN] Sodium-dependent amino acids transporter that has a broad substrate specificity, with a preference for zwitterionic amino acids. It accepts as substrates all neutral amino acids, including glutamine, asparagine, and branched-chain and aromatic amino acids, and excludes methylated, anionic, and cationic amino acids (PubMed:8702519). Through binding of the fusogenic protein syncytin-1/ERVW-1 may mediate trophoblasts syncytialization, the spontaneous fusion of their plasma membranes, an essential process in placental development (PubMed:10708449, PubMed:23492904).[1] [2] [3] (Microbial infection) Acts as a cell surface receptor for Feline endogenous virus RD114.[4] [5] (Microbial infection) Acts as a cell surface receptor for Baboon M7 endogenous virus.[6] (Microbial infection) Acts as a cell surface receptor for type D simian retroviruses.[7] Publication Abstract from PubMedThe 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. A one-gate elevator mechanism for the human neutral amino acid transporter ASCT2.,Garaeva AA, Guskov A, Slotboom DJ, Paulino C Nat Commun. 2019 Jul 31;10(1):3427. doi: 10.1038/s41467-019-11363-x. PMID:31366933[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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