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

Alisa Garaeva, Gerrit Oostergetel, Cornelius Gati, Albert Guskov, Cristina Batista Paulino, Dirk Slotboom*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

47 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)515-521
JournalNature Structural & Molecular Biology
Volume25
DOIs
Publication statusPublished - 5-Jun-2018

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