title: Structure of BamA, an essential factor in outer membrane protein biogenesis.
abstract: Outer membrane protein (OMP) biogenesis is an essential process for maintaining the bacterial cell envelope and involves the β-barrel assembly machinery (BAM) for OMP recognition, folding and assembly. In Escherichia coli this function is orchestrated by five proteins: the integral outer membrane protein BamA of the Omp85 superfamily and four associated lipoproteins. To unravel the mechanism underlying OMP folding and insertion, the structure of the E. coli BamA β-barrel and P5 domain was determined at 3 Å resolution. These data add information beyond that provided in the recently published crystal structures of BamA from Haemophilus ducreyi and Neisseria gonorrhoeae and are a valuable basis for the interpretation of pertinent functional studies. In an `open' conformation, E. coli BamA displays a significant degree of flexibility between P5 and the barrel domain, which is indicative of a multi-state function in substrate transfer. E. coli BamA is characterized by a discontinuous β-barrel with impaired β1-β16 strand interactions denoted by only two connecting hydrogen bonds and a disordered C-terminus. The 16-stranded barrel surrounds a large cavity which implies a function in OMP substrate binding and partial folding. These findings strongly support a mechanism of OMP biogenesis in which substrates are partially folded inside the barrel cavity and are subsequently released laterally into the lipid bilayer.
authors.affiliation: Department of Protein Evolution, Max-Planck-Institut für Entwicklungsbiologie, Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Albrecht
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Schütz
authors.affiliation: Institut für Medizinische Mikrobiologie und Hygiene, Elfriede-Aulhorn-Strasse 6, 72076 Tübingen, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Oberhettinger
authors.affiliation: Department for Microbiology, Biocenter of the University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Faulstich
authors.affiliation: Unidad de Biofisica (CSIC-UPV/EHU), Barrio Sarriena s/n, 48940 Leioa, Vizcaya, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bermejo
authors.affiliation: Department for Microbiology, Biocenter of the University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rudel
authors.affiliation: Department of Biology, University of Konstanz, 78457 Konstanz, Germany.
authors.forename: Kay
authors.initials: K
authors.lastname: Diederichs
authors.affiliation: Department of Protein Evolution, Max-Planck-Institut für Entwicklungsbiologie, Spemannstrasse 35, 72076 Tübingen, Germany.
authors.forename: Kornelius
authors.initials: K
authors.lastname: Zeth
mesh_terms: D000595:Amino Acid Sequence; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid
chemical_list: D001425:Bacterial Outer Membrane Proteins; C503914:BamA protein, E coli; D029968:Escherichia coli Proteins
keywords: BAM complex; BamA; OMP insertion; POTRA; insertase