2. Academic Validation
  3. Cryo-EM structure of the human neutral amino acid transporter ASCT2

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.
Alisa A Garaeva 1,  Gert T Oostergetel 2,  Cornelius Gati 3 4,  Albert Guskov 5,  Cristina Paulino 6,  Dirk J Slotboom 7 8
Affiliations

Affiliations

  • 1 University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, Membrane Enzymology, Groningen, the Netherlands.
  • 2 University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, Structural Biology, Groningen, the Netherlands.
  • 3 SLAC National Accelerator Laboratory, Bioscience Division, Menlo Park, CA, USA.
  • 4 Stanford University, Department of Structural Biology, Stanford, CA, USA.
  • 5 University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, Structural Biology, Groningen, the Netherlands. [email protected].
  • 6 University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, Structural Biology, Groningen, the Netherlands. [email protected].
  • 7 University of Groningen, Groningen Biomolecular Sciences and Biotechnology Institute, Membrane Enzymology, Groningen, the Netherlands. [email protected].
  • 8 University of Groningen, Zernike Institute for Advanced Materials, Groningen, the Netherlands. [email protected].
PMID: 29872227 DOI: 10.1038/s41594-018-0076-y
Abstract

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.

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