PDBsum entry 4c48

Transport protein

PDB id: 4c48

Contents

Protein chains

1032 a.a.

152 a.a.

46 a.a.

Ligands

LMT ×9

Metals

_NI

Waters ×35

PDB id:

4c48

Name:

Transport protein

Title:

Crystal structure of acrb-acrz complex

Structure:

Acriflavine resistance protein b. Chain: a. Fragment: residues 1-1047. Synonym: acrb. Engineered: yes. Darpin. Chain: b. Engineered: yes. Uncharacterized membrane protein ybht.

Source:

Escherichia coli k-12. Organism_taxid: 83333. Variant: novablue. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008. Expression_system_variant: c43. Other_details: novagen. Synthetic construct. Organism_taxid: 32630.

Resolution:

3.30Å R-factor: 0.283 R-free: 0.322

Authors:

D.Du,N.James,E.Klimont,B.F.Luisi

Key ref:

D.Du et al. (2014). Structure of the AcrAB-TolC multidrug efflux pump. Nature, 509, 512-515. PubMed id: 24747401 DOI: 10.1038/nature13205

Date:

02-Sep-13 Release date: 30-Apr-14

Protein chain

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

Seq: 1049 a.a.

Struc: 1032 a.a.

Protein chain

No UniProt id for this chain

Struc: 152 a.a.

Protein chain

P0AAW9  (ACRZ_ECOLI) -  Multidrug efflux pump accessory protein AcrZ from Escherichia coli (strain K12)

Seq: 49 a.a.

Struc: 46 a.a.

DOI no: 10.1038/nature13205

Nature 509:512-515 (2014)

PubMed id: 24747401

Structure of the AcrAB-TolC multidrug efflux pump.

D.Du, Z.Wang, N.R.James, J.E.Voss, E.Klimont, T.Ohene-Agyei, H.Venter, W.Chiu, B.F.Luisi.

ABSTRACT

The capacity of numerous bacterial species to tolerate antibiotics and other toxic compounds arises in part from the activity of energy-dependent transporters. In Gram-negative bacteria, many of these transporters form multicomponent 'pumps' that span both inner and outer membranes and are driven energetically by a primary or secondary transporter component. A model system for such a pump is the acridine resistance complex of Escherichia coli. This pump assembly comprises the outer-membrane channel TolC, the secondary transporter AcrB located in the inner membrane, and the periplasmic AcrA, which bridges these two integral membrane proteins. The AcrAB-TolC efflux pump is able to transport vectorially a diverse array of compounds with little chemical similarity, thus conferring resistance to a broad spectrum of antibiotics. Homologous complexes are found in many Gram-negative species, including in animal and plant pathogens. Crystal structures are available for the individual components of the pump and have provided insights into substrate recognition, energy coupling and the transduction of conformational changes associated with the transport process. However, how the subunits are organized in the pump, their stoichiometry and the details of their interactions are not known. Here we present the pseudo-atomic structure of a complete multidrug efflux pump in complex with a modulatory protein partner from E. coli. The model defines the quaternary organization of the pump, identifies key domain interactions, and suggests a cooperative process for channel assembly and opening. These findings illuminate the basis for drug resistance in numerous pathogenic bacterial species.