title: Structure of the periplasmic adaptor protein from a major facilitator superfamily (MFS) multidrug efflux pump.
abstract: Periplasmic adaptor proteins are key components of bacterial tripartite efflux pumps. The 2.85 Å resolution structure of an MFS (major facilitator superfamily) pump adaptor, Aquifex aeolicus EmrA, shows linearly arranged α-helical coiled-coil, lipoyl, and β-barrel domains, but lacks the fourth membrane-proximal domain shown in other pumps to interact with the inner membrane transporter. The adaptor α-hairpin, which binds outer membrane TolC, is exceptionally long at 127 Å, and the β-barrel contains a conserved disordered loop. The structure extends the view of adaptors as flexible, modular components that mediate diverse pump assembly, and suggests that in MFS tripartite pumps a hexamer of adaptors could provide a periplasmic seal.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Philip
authors.initials: P
authors.lastname: Hinchliffe
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.affiliation: Diamond Light Source, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.
authors.forename: Neil G
authors.initials: NG
authors.lastname: Paterson
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Allister
authors.initials: A
authors.lastname: Crow
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
authors.forename: Colin
authors.initials: C
authors.lastname: Hughes
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK. Electronic address: vk103@cam.ac.uk.
authors.forename: Vassilis
authors.initials: V
authors.lastname: Koronakis
mesh_terms: D000595:Amino Acid Sequence; D029063:Aquifoliaceae; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D017124:Conserved Sequence; D018360:Crystallography, X-Ray; D008024:Ligands; D026901:Membrane Transport Proteins / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D001426:Bacterial Proteins; D008024:Ligands; D026901:Membrane Transport Proteins
keywords: Adaptor protein; Antibiotic resistance; Crystal structure; Major facilitator superfamily; Multidrug efflux