| 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 |
42.779
|
| Times Cited |
21
|
|
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 |
|
