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[beta]-barrel membrane proteins are essential for nutrient import, signalling, motility and survival. In Gram-negative bacteria, the [beta]-barrel assembly machinery (BAM) complex is responsible for the biogenesis of [beta]-barrel membrane proteins, with homologous complexes found in mitochondria and chloroplasts. Here we describe the structure of BamA, the central and essential component of the BAM complex, from two species of bacteria: Neisseria gonorrhoeae and Haemophilus ducreyi. BamA consists of a large periplasmic domain attached to a 16-strand transmembrane [beta]-barrel domain. Three structural features shed light on the mechanism by which BamA catalyses [beta]-barrel assembly. First, the interior cavity is accessible in one BamA structure and conformationally closed in the other. Second, an exterior rim of the [beta]-barrel has a distinctly narrowed hydrophobic surface, locally destabilizing the outer membrane. And third, the [beta]-barrel can undergo lateral opening, suggesting a route from the interior cavity in BamA into the outer membrane. The crystal structure of BamA, the central component of the [beta]-barrel assembly machinery (BAM) complex, from N. gonorrhoeae and H. ducreyi is determined; the structure consists of an interior cavity capped by extracellular loops, an exterior rim with a narrowed hydrophobic surface and a lateral opening of the barrel domain, providing insight into a possible route for the insertion of [beta]-barrel membrane proteins into the bacterial outer membrane. Structure of key bacterial membrane protein In Gram-negative bacteria, the [beta]-barrel assembly machinery (BAM) complex is responsible for the biogenesis of [beta]-barrel membrane proteins, which are essential for nutrient import, signalling, motility and survival. BamA and its homologues are recognized as potentially important therapeutic targets for new drugs and vaccines. Here Susan Buchanan and colleagues report the crystal structure of BamA, the central component of the BAM complex, from Neisseria gonorrhoeae and Haemophilus ducreyi. Features including an interior cavity, an exterior rim with a narrowed hydrophobic surface and a lateral opening of the ring provide a glimpse of a possible route for the insertion of [beta]-barrel membrane proteins into the bacterial outer membrane., Author(s): Nicholas Noinaj [sup.1] , Adam J. Kuszak [sup.1] , James C. Gumbart [sup.2] , Petra Lukacik [sup.3] , Hoshing Chang [sup.1] , Nicole C. Easley [sup.1] , Trevor Lithgow [...]

Neisseria are obligate human pathogens causing bacterial meningitis, septicaemia and gonorrhoea. Neisseria require iron for survival and can extract it directly from human transferrin for transport across the outer membrane. The transport system consists of TbpA, an integral outer membrane protein, and TbpB, a co- receptor attached to the cell surface; both proteins are potentially important vaccine and therapeutic targets. Two key questions driving Neisseria research are how human transferrin is specifically targeted, and how the bacteria liberate iron from transferrin at neutral pH. To address these questions, we solved crystal structures of the TbpA-transferrin complex and of the corresponding co-receptor TbpB. We characterized the TbpB-transferrin complex by small-angle X-ray scattering and the TbpA-TbpB-transferrin complex by electron microscopy. Our studies provide a rational basis for the specificity of TbpA for human transferrin, show how TbpA promotes iron release from transferrin, and elucidate how TbpB facilitates this process., Neisseria comprise a large family of Gram-negative bacteria that colonize humans. Two family members, Neisseria gonorrhoeae and Neisseria meningitidis, are pathogens that invade the urogenital tract and nasopharynx, respectively, causing [...]