PDBsum entry 2dhh

Membrane protein

PDB id: 2dhh

Contents

Protein chains

1022 a.a. *

Waters ×56

* Residue conservation analysis

PDB id:

2dhh

Name:

Membrane protein

Title:

Crystal structure of a multidrug transporter reveal a functionally rotating mechanism

Structure:

Acrb. Chain: a, b, c. Synonym: multidrug efflux transporter, acriflavine resistance protein b. Engineered: yes

Source:

Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli k12. Expression_system_taxid: 83333.

Biol. unit:

Trimer (from PQS)

Resolution:

2.80Å R-factor: 0.270 R-free: 0.307

Authors:

S.Murakami,R.Nakashima,E.Yamashita,T.Matsumoto

Key ref:

S.Murakami et al. (2006). Crystal structures of a multidrug transporter reveal a functionally rotating mechanism. Nature, 443, 173-179. PubMed id: 16915237 DOI: 10.1038/nature05076

Date:

23-Mar-06 Release date: 22-Aug-06

Protein chains

P31224  (ACRB_ECOLI) -  Multidrug efflux pump subunit AcrB from Escherichia coli (strain K12)

Seq: 1049 a.a.

Struc: 1022 a.a.

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1038/nature05076

Nature 443:173-179 (2006)

PubMed id: 16915237

Crystal structures of a multidrug transporter reveal a functionally rotating mechanism.

S.Murakami, R.Nakashima, E.Yamashita, T.Matsumoto, A.Yamaguchi.

ABSTRACT

AcrB is a principal multidrug efflux transporter in Escherichia coli that cooperates with an outer-membrane channel, TolC, and a membrane-fusion protein, AcrA. Here we describe crystal structures of AcrB with and without substrates. The AcrB-drug complex consists of three protomers, each of which has a different conformation corresponding to one of the three functional states of the transport cycle. Bound substrate was found in the periplasmic domain of one of the three protomers. The voluminous binding pocket is aromatic and allows multi-site binding. The structures indicate that drugs are exported by a three-step functionally rotating mechanism in which substrates undergo ordered binding change.

Selected figure(s)

Figure 3.
Figure 3: The novel drug translocation pathway for AcrB.
Figure 3 : The novel drug translocation pathway for AcrB. Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, or to obtain a text description, please contact npg@nature.com-
Bound minocycline in the binding protomer is shown in a CPK representation and coloured as in Fig. 1. a, Stereo-pair of the inner cavities inside the periplasmic region of AcrB viewed from the side parallel to the membrane plane as in Fig. 1a. The chicken-wire representation coloured in magenta is the solvent-accessible inner cavity of the AcrB molecule created with the program VOIDOO^42 and MAMA^43 of the Uppsala Software Factory (http://xray.bmc.uu.se/usf/) with slight modifications (surface-noise removal, and so on). For clarity, the access protomer is removed. b, Close-up stereo views of the vestibules in three different transport states, viewed from slightly diagonally below to the side of the molecule. Three protomers are superposed using the least-squares superposition program LSQKAB, from the CCP4 program suite^33. The flexible region above TM8 and the PC2 subdomain are represented by solid colours corresponding to the colours in Fig. 1, and the remaining main-chain tracings are more transparent. The vestibule is indicated as a dotted circle.

Figure 4.
Figure 4: Structure with a slab ( approx-23 Å) of the transmembrane domain viewed from the periplasmic side. The side chains of three functionally essential charged residues—Asp 407, Asp 408 and Lys 940—and functionally important residue Thr 978 are shown in a ball-and-stick representation. Colours of the protomers are as in Fig. 1. Roman numerals indicate the transmembrane helix numbers^13.

The above figures are reprinted by permission from Macmillan Publishers Ltd: Nature (2006, 443, 173-179) copyright 2006.

Figures were selected by an automated process.