Membrane protein architects: the role of the BAM complex in outer membrane protein assembly

• Published in: Nature reviews. Microbiology 2009-03, Vol.7 (3), p.206-214
• Main Authors: Henderson, Ian R, Knowles, Timothy J, Scott-Tucker, Anthony, Overduin, Michael
• Format: Article
• Language: English
• Subjects: Bacteria; Bacterial Outer Membrane Proteins - chemistry; Bacterial Outer Membrane Proteins - metabolism; Biomedical and Life Sciences; Escherichia coli; Escherichia coli Proteins - chemistry; Escherichia coli Proteins - metabolism; Genetic aspects; Gram-Negative Bacteria - chemistry; Gram-Negative Bacteria - metabolism; Infectious Diseases; Life Sciences; Medical Microbiology; Membrane proteins; Membranes; Microbiology; Models, Molecular; Molecular Chaperones - metabolism; Parasitology; Physiological aspects; Protein Folding; Protein Multimerization; Protein Transport; Proteins; review-article; Virology
• ISSN: 1740-1526; 1740-1534
• DOI: 10.1038/nrmicro2069

Key Points The Gram-negative outer membrane protein (OMP) family includes proteins that are associated with basic physiological functions, virulence and multidrug resistance, and therefore plays a fundamental part in the maintenance of cellular viability. Understanding how these proteins are targeted and folded into this membrane is crucial, as it could offer important medical benefits. Compounds that inhibit key stages of this process would block key stages of OMP biogenesis, thereby inhibiting essential physiological, pathogenic and drug resistance functions, and could prove useful in combating diverse pathogens, including Pseudomonas aeruginosa , Neisseria meningitidis and Salmonella enterica . OMP biogenesis in Gram-negative bacteria has, until recently, remained a largely unknown mechanism. However, over the past 3 years, a complex of proteins has been discovered that is known as the β-barrel assembly machinery (BAM) and is responsible for folding and inserting OMPs into the membrane. Recent advances in our understanding of the molecular basis of OMP biogenesis in Gram-negative bacteria are discussed. Emphasis is placed on analysis of the recently discovered component structures and accessory interactions, in particular with the periplasmic chaperones DegP, Skp and SurA, which are known to interact with OMPs. The mechanisms that the BAM complex might use in the folding and insertion of OMPs into the membrane are also discussed. Considerable advances have been made in the field of outer membrane protein biogenesis during the past year. The β-barrel assembly machinery (BAM) mediates efficient insertion of folded β-barrels into the outer membrane of Gram-negative bacteria. The role of the BAM in the folding of membrane proteins is discussed in this Review. The folding of transmembrane proteins into the outer membrane presents formidable challenges to Gram-negative bacteria. These proteins must migrate from the cytoplasm, through the inner membrane and into the periplasm, before being recognized by the β-barrel assembly machinery, which mediates efficient insertion of folded β-barrels into the outer membrane. Recent discoveries of component structures and accessory interactions of this complex are yielding insights into how cells fold membrane proteins. Here, we discuss how these structures illuminate the mechanisms responsible for the biogenesis of outer membrane proteins.