title: Architecture and roles of periplasmic adaptor proteins in tripartite eﬄux assemblies.
abstract: Recent years have seen major advances in the structural understanding of the different components of tripartite eﬄux assemblies, which encompass the multidrug eﬄux (MDR) pumps and type I secretion systems. The majority of these investigations have focused on the role played by the inner membrane transporters and the outer membrane factor (OMF), leaving the third component of the system - the Periplasmic Adaptor Proteins (PAPs) - relatively understudied. Here we review the current state of knowledge of these versatile proteins which, far from being passive linkers between the OMF and the transporter, emerge as active architects of tripartite assemblies, and play diverse roles in the transport process. Recognition between the PAPs and OMFs is essential for pump assembly and function, and targeting this interaction may provide a novel avenue for combating multidrug resistance. With the recent advances elucidating the drug eﬄux and energetics of the tripartite assemblies, the understanding of the interaction between the OMFs and PAPs is the last piece remaining in the complete structure of the tripartite pump assembly puzzle.
authors.affiliation: Department of Veterinary Medicine, University of Cambridge Cambridge, UK.
authors.forename: Martyn F
authors.initials: MF
authors.lastname: Symmons
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham Birmingham, UK.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Marshall
authors.affiliation: Institute of Microbiology and Infection, University of Birmingham Birmingham, UK.
authors.forename: Vassiliy N
authors.initials: VN
authors.lastname: Bavro
keywords: RND family pumps; TolC; antibiotic resistance; drug eﬄux pumps; membrane proteins; membrane transport; periplasmic adaptor proteins; type I secretion system