6mpb | pdb_00006mpb
Cryo-EM structure of the human neutral amino acid transporter ASCT2
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 PubMedAlanine-serine-cysteine transporter 2 (ASCT2, SLC1A5) is the primary transporter of glutamine in cancer cells and regulates the mTORC1 signaling pathway. The SLC1A5 function involves finely tuned orchestration of two domain movements that include the substrate-binding transport domain and the scaffold domain. Here, we present cryo-EM structures of human SLC1A5 and its complex with the substrate, L-glutamine in an outward-facing conformation. These structures reveal insights into the conformation of the critical ECL2a loop which connects the two domains, thus allowing rigid body movement of the transport domain throughout the transport cycle. Furthermore, the structures provide new insights into substrate recognition, which involves conformational changes in the HP2 loop. A putative cholesterol binding site was observed near the domain interface in the outward-facing state. Comparison with the previously determined inward-facing structure of SCL1A5 provides a basis for a more integrated understanding of substrate recognition and transport mechanism in the SLC1 family. Cryo-EM structures of the human glutamine transporter SLC1A5 (ASCT2) in the outward-facing conformation.,Yu X, Plotnikova O, Bonin PD, Subashi TA, McLellan TJ, Dumlao D, Che Y, Dong YY, Carpenter EP, West GM, Qiu X, Culp JS, Han S Elife. 2019 Oct 3;8. pii: 48120. doi: 10.7554/eLife.48120. PMID:31580259[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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