PDBsum entry 2f2m

Transport protein

PDB id: 2f2m

Contents

Protein chains

106 a.a.

Ligands

P4P

Obsolete entry

PDB id:

2f2m

Name:

Transport protein

Title:

X-ray crystal structure of the emre multidrug transporter in complex with tpp

Structure:

Protein emre. Chain: a, b. Synonym: methyl viologen resistance protein c, ethidium resistance protein. Engineered: yes

Source:

Escherichia coli. Bacteria. Gene: emre, eb, mvrc. Expressed in: escherichia coli.

Biol. unit:

Tetramer (from PQS)

Resolution:

3.70Å R-factor: 0.282 R-free: 0.354

Authors:

O.Pornillos,Y.J.Chen,A.P.Chen,G.Chang

Key ref:

O.Pornillos et al. (2005). X-ray structure of the EmrE multidrug transporter in complex with a substrate. Science, 310, 1950-1953. PubMed id: 16373573 DOI: 10.1126/science.1119776

Date:

17-Nov-05 Release date: 27-Dec-05

Protein chains

P23895  (EMRE_ECOLI) -  Multidrug transporter EmrE

Seq: 110 a.a.

Struc: 106 a.a.

DOI no: 10.1126/science.1119776

Science 310:1950-1953 (2005)

PubMed id: 16373573

X-ray structure of the EmrE multidrug transporter in complex with a substrate.

O.Pornillos, Y.J.Chen, A.P.Chen, G.Chang.

ABSTRACT

EmrE is a prototype of the Small Multidrug Resistance family of efflux transporters and actively expels positively charged hydrophobic drugs across the inner membrane of Escherichia coli. Here, we report the x-ray crystal structure, at 3.7 angstrom resolution, of one conformational state of the EmrE transporter in complex with a translocation substrate, tetraphenylphosphonium. Two EmrE polypeptides form a homodimeric transporter that binds substrate at the dimerization interface. The two subunits have opposite orientations in the membrane and adopt slightly different folds, forming an asymmetric antiparallel dimer. This unusual architecture likely confers unidirectionality to transport by creating an asymmetric substrate translocation pathway. On the basis of available structural data, we propose a model for the proton-dependent drug efflux mechanism of EmrE.

Selected figure(s)

Figure 3.
Fig. 3. Comparison of the x-ray and EM structures of EmrE-TPP. (A) Independent superposition of EmrE subunits A and B in the x-ray structure with a cylinder model (colored gray) derived from the EM structure of EmrE-TPP (European Molecular Biology Laboratory-EBI accession code EMD-1087) (13). A unique match was found using two constraints: Three-helix bundles on opposite sides of the dimer were assumed to be helices 1 to 3, and the helix closest to the density attributed to TPP in the EM map was assumed to be helix 1. In this pseudo-atomic model, three helices have notably different tilt angles: A2, B2, and B3 (shown by red asterisks). The x-ray position of helices B2 and B3, which appear to move as a unit, is likely due to crystal packing interactions along the putative tetramerization interface (see also Fig. 1E). We speculate that the conformational change in helix A2 is relevant to the drug transport mechanism. (B and C) The TPP molecule is bound to different sites in the x-ray structure (C) and EM model (B), suggesting a possible mechanism for drug transport. The relative positions of the EmrE helices are indicated, viewing toward the binding pockets (in the same orientation as in Fig. 1C). The positions of the TPP molecules are shown by red circles.

Figure 4.
Fig. 4. A potential mechanism for proton-dependent drug translocation by EmrE. For clarity, only the three putative gating helices (A1, A2, and B1) and two membrane-embedded Glu-14 side chains are shown explicitly. Drug substrates and protons are represented by the yellow sphere and red balls, respectively.

The above figures are reprinted by permission from the AAAs: Science (2005, 310, 1950-1953) copyright 2005.

Figures were selected by the author.

Author's comment

Retracted by Chang et al. (2006) Science, 314, 187.