Structural basis for amino acid export by dmt superfamily transporter yddg.

• Autores: Hirotoshi Tsuchiya, Shintaro Doki, Mizuki Takemoto, Tatsuya Ikuta, Keita Fukui, Yoshihiro Usuda
• Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 534, Nº 7607, 2016, págs. 417-420
• Idioma: inglés
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• Resumen

  • The drug/metabolite transporter (DMT) superfamily is a large group of membrane transporters ubiquitously found in eukaryotes, bacteria and archaea, and includes exporters for a remarkably wide range of substrates, such as toxic compounds and metabolites 1. YddG is a bacterial DMT protein that expels aromatic amino acids and exogenous toxic compounds, thereby contributing to cellular homeostasis 2,3. Here we present structural and functional analyses of YddG. Using liposome-based analyses, we show that Escherichia coli and Starkeya novella YddG export various amino acids. The crystal structure of S. novella YddG at 2.4 A resolution reveals a new membrane transporter topology, with ten transmembrane segments in an outward-facing state. The overall structure is basket-shaped, with a large substrate-binding cavity at the centre of the molecule, and is composed of inverted structural repeats related by two-fold pseudo-symmetry. On the basis of this intramolecular symmetry, we propose a structural model for the inward-facing state and a mechanism of the conformational change for substrate transport, which we confirmed by biochemical analyses. These findings provide a structural basis for the mechanism of transport of DMT superfamily proteins.