Journal Article

Structural insight into the biogenesis of β-barrel membrane proteins

Easley, Nicole C., Kuszak, Adam J., Gumbart, James C., Noinaj, Nicholas, Chang, Hoshing, Lithgow, Trevor, Lukacik, Petra, Buchanan, Susan K.

2013

Overview

β-barrel membrane proteins are essential for nutrient import, signalling, motility and survival. In Gram-negative bacteria, the β-barrel assembly machinery (BAM) complex is responsible for the biogenesis of β-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 β-barrel domain. Three structural features shed light on the mechanism by which BamA catalyses β-barrel assembly. First, the interior cavity is accessible in one BamA structure and conformationally closed in the other. Second, an exterior rim of the β-barrel has a distinctly narrowed hydrophobic surface, locally destabilizing the outer membrane. And third, the β-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 β-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 β-barrel membrane proteins into the bacterial outer membrane. Structure of key bacterial membrane protein In Gram-negative bacteria, the β-barrel assembly machinery (BAM) complex is responsible for the biogenesis of β-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 β-barrel membrane proteins into the bacterial outer membrane.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/326/41/2180 / 631/45/470 / 631/535/1266 / Bacterial Outer Membrane Proteins - biosynthesis / Bacterial Outer Membrane Proteins - chemistry / Bacterial Outer Membrane Proteins - genetics / Biosynthesis / Cell Membrane - chemistry / Cell Membrane - metabolism / Crystallography, X-Ray / Escherichia coli - chemistry / Escherichia coli - genetics / Escherichia coli Proteins - chemistry / Escherichia coli Proteins - genetics / Haemophilus - chemistry / Humanities and Social Sciences / Hydrophobic and Hydrophilic Interactions / Membrane proteins / Models, Molecular / multidisciplinary / Mutagenesis / Neisseria gonorrhoeae - chemistry / Physiological aspects / Protein Conformation / Proteins / Science / Structural Homology, Protein / Structure