Structural basis for xenobiotic extrusion by eukaryotic MATE transporter

Nat Commun. 2017 Nov 21;8(1):1633. doi: 10.1038/s41467-017-01541-0.


Mulitidrug and toxic compound extrusion (MATE) family transporters export xenobiotics to maintain cellular homeostasis. The human MATE transporters mediate the excretion of xenobiotics and cationic clinical drugs, whereas some plant MATE transporters are responsible for aluminum tolerance and secondary metabolite transport. Here we report the crystal structure of the eukaryotic MATE transporter from Arabidopsis thaliana, at 2.6 Å resolution. The structure reveals that its carboxy-terminal lobe (C-lobe) contains an extensive hydrogen-bonding network with well-conserved acidic residues, and their importance is demonstrated by the structure-based mutational analysis. The structural and functional analyses suggest that the transport mechanism involves the structural change of transmembrane helix 7, induced by the formation of a hydrogen-bonding network upon the protonation of the conserved acidic residue in the C-lobe. Our findings provide insights into the transport mechanism of eukaryotic MATE transporters, which is important for the improvement of the pharmacokinetics of the clinical drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arabidopsis / chemistry
  • Arabidopsis / genetics
  • Arabidopsis / metabolism*
  • Arabidopsis Proteins / chemistry*
  • Arabidopsis Proteins / genetics
  • Arabidopsis Proteins / metabolism
  • Biological Transport
  • Gene Expression Regulation, Plant
  • Humans
  • Organic Cation Transport Proteins / chemistry*
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism
  • Protein Domains
  • Xenobiotics / metabolism*


  • Arabidopsis Proteins
  • DTX14 protein, Arabidopsis
  • Organic Cation Transport Proteins
  • SLC47A1 protein, human
  • Xenobiotics