RRC ID 39654
Author Tsuchiya H, Doki S, Takemoto M, Ikuta T, Higuchi T, Fukui K, Usuda Y, Tabuchi E, Nagatoishi S, Tsumoto K, Nishizawa T, Ito K, Dohmae N, Ishitani R, Nureki O.
Title Structural basis for amino acid export by DMT superfamily transporter YddG.
Journal Nature
Abstract 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. YddG is a bacterial DMT protein that expels aromatic amino acids and exogenous toxic compounds, thereby contributing to cellular homeostasis. 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 Å 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.
Volume 534(7607)
Pages 417-20
Published 2016-6-16
DOI 10.1038/nature17991
PII nature17991
PMID 27281193
MeSH Alphaproteobacteria / chemistry Alphaproteobacteria / metabolism Amino Acid Transport Systems, Neutral / chemistry* Amino Acid Transport Systems, Neutral / metabolism* Amino Acids / metabolism* Biological Transport Crystallography, X-Ray Escherichia coli / chemistry Escherichia coli / metabolism Escherichia coli Proteins / chemistry* Escherichia coli Proteins / metabolism* Liposomes / chemistry Liposomes / metabolism Models, Molecular Protein Conformation Structure-Activity Relationship
IF 41.577
Times Cited 1
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
DNA material Genomic DNA of Starkeya novella JCM 20403T (JGD08351) Genomic DNA of Escherichia coli JCM 20135 (JGD07547).
General Microbes