"Machinery of drug transport in Escherichia coli and related bacteria"
Microorganisms encode several classes of transmembrane molecular pumps
that can expel a wide range of chemically distinct toxic substances.
These machines contribute to the capacity of the organisms to withstand
harsh environments, and they help to confer resistance against clinical
antimicrobial agents. In Gram-negative bacteria, the pumps comprise
tripartite assemblies that actively transport drugs and other harmful
compounds across the cell envelope. We describe recent structural and
functional data that have provided insights into the architecture and
transport mechanism of the AcrA-AcrB-TolC pump of Escherichia coli. This
multi-drug efflux pump is powered by AcrB, a member of the
resistance/nodulation/cell division (RND) family of transporters, which
are energised by proton electrochemical gradients. Crystallographic data
reveal how a small protein AcrZ is engaged in a concave surface in the
transmembrane domain of AcrB, and we discuss how this interaction may
affect the efflux activities of AcrB and other RND family members.

[1] Du, D., Wang, Z., James, N.R., Voss, J.E., Klimont, E., Ohene-Agyei,
T., Venter, H. Chiu, W. and Luisi, B.F. (2014). Structure of the
AcrAB-TolC multidrug efflux pump. Nature. 509, 512-515.
[2] Du, D., van Veen, H.W., Murakami, S., Pos, K.M. and Luisi, B.F.
(2015). Structure, mechanism and cooperation of bacterial multidrug
transporters. Current Opin. Struct. Biol . doi:
10.1016/j.sbi.2015.07.015 PMID 26282926.
Date: 12 February 2016, 11:00 (Friday, 4th week, Hilary 2016)
Venue: Wellcome Trust Centre for Human Genetics, Headington OX3 7BN
Venue Details: Meeting Rooms A & B
Speaker: Prof Ben Luisi (Department of Biochemistry, University of Cambridge)
Organising department: Division of Structural Biology
Organiser: Eleanor Martin (Wellcome Trust Centre for Human Genetics)
Organiser contact email address: jones-pa@strubi.ox.ac.uk
Hosts: Prof E.Yvonne Jones (University of Oxford), Prof David Stuart (University of Oxford)
Part of: Strubi seminars
Booking required?: Not required
Audience: Members of the University only
Editors: Eleanor Martin, Agata Krupa