title: Structure of an atypical periplasmic adaptor from a multidrug efflux pump of the spirochete Borrelia burgdorferi.
abstract: Periplasmic adaptor proteins are essential components of bacterial tripartite multidrug efflux pumps. Here we report the 2.35 Å resolution crystal structure of the BesA adaptor from the spirochete Borrelia burgdorferi solved using selenomethionine derivatized protein. BesA shows the archetypal linear, flexible, multi-domain architecture evident among proteobacteria and retains the lipoyl, β-barrel and membrane-proximal domains that interact with the periplasmic domains of the inner membrane transporter. However, it lacks the α-hairpin domain shown to establish extensive coiled-coil interactions with the periplasmic entrance helices of the outer membrane-anchored TolC exit duct. This has implications for the modelling of assembled tripartite efflux pumps.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Greene
authors.forename: Philip
authors.initials: P
authors.lastname: Hinchliffe
authors.forename: Allister
authors.initials: A
authors.lastname: Crow
authors.forename: Abdessamad
authors.initials: A
authors.lastname: Ababou
authors.forename: Colin
authors.initials: C
authors.lastname: Hughes
authors.forename: Vassilis
authors.initials: V
authors.lastname: Koronakis
mesh_terms: D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D004926:Escherichia coli / Q000235:genetics; D015870:Gene Expression; D056004:Molecular Dynamics Simulation; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D019897:Periplasm / Q000737:chemistry*; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012645:Selenomethionine / Q000737:chemistry / Q000378:metabolism
chemical_list: D001425:Bacterial Outer Membrane Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011994:Recombinant Proteins; D012645:Selenomethionine
keywords: Adaptor protein; Antibiotic resistance; Crystal structure; HME; IM; MD; MDR; MP; Multidrug efflux; OM; RMSDs; heavy metal efflux; inner membrane; membrane proximal; molecular dynamics; multidrug resistance; outer membrane; root mean square deviations