Cryo-EM structure of the human neutral amino acid transporter ASCT2

Nat Struct Mol Biol. 2018 Jun;25(6):515-521. doi: 10.1038/s41594-018-0076-y. Epub 2018 Jun 5.


Human ASCT2 belongs to the SLC1 family of secondary transporters and is specific for the transport of small neutral amino acids. ASCT2 is upregulated in cancer cells and serves as the receptor for many retroviruses; hence, it has importance as a potential drug target. Here we used single-particle cryo-EM to determine a structure of the functional and unmodified human ASCT2 at 3.85-Å resolution. ASCT2 forms a homotrimeric complex in which each subunit contains a transport and a scaffold domain. Prominent extracellular extensions on the scaffold domain form the predicted docking site for retroviruses. Relative to structures of other SLC1 members, ASCT2 is in the most extreme inward-oriented state, with the transport domain largely detached from the central scaffold domain on the cytoplasmic side. This domain detachment may be required for substrate binding and release on the intracellular side of the membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Transport System ASC / chemistry*
  • Amino Acid Transport System ASC / genetics
  • Amino Acid Transport System ASC / metabolism
  • Amino Acid Transport System ASC / ultrastructure
  • Binding Sites
  • Cryoelectron Microscopy / methods*
  • Crystallography, X-Ray
  • Glutamine / metabolism
  • Humans
  • Minor Histocompatibility Antigens / chemistry*
  • Minor Histocompatibility Antigens / genetics
  • Minor Histocompatibility Antigens / metabolism
  • Minor Histocompatibility Antigens / ultrastructure
  • Pichia / genetics
  • Protein Conformation
  • Protein Domains
  • Protein Folding
  • Protein Transport
  • Proteolipids / metabolism
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / ultrastructure


  • Amino Acid Transport System ASC
  • Minor Histocompatibility Antigens
  • Proteolipids
  • Recombinant Proteins
  • SLC1A5 protein, human
  • proteoliposomes
  • Glutamine