Bakelar Jeremy, Buchanan Susan K, Noinaj Nicholas
Department of Biological Sciences, Markey Center for Structural Biology, Purdue Institute for Inflammation, Immunology and Infectious Diseases, Purdue University, West Lafayette, IN, USA.
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
FEBS J. 2017 Jun;284(12):1778-1786. doi: 10.1111/febs.13960. Epub 2016 Nov 29.
The β-barrel assembly machinery (BAM) is a multicomponent complex responsible for the biogenesis of β-barrel outer membrane proteins (OMPs) in Gram-negative bacteria, with conserved systems in both mitochondria and chloroplasts. Given its importance in the integrity of the outer membrane and in the assembly of surface exposed virulence factors, BAM is an attractive therapeutic target against pathogenic bacteria, particularly multidrug-resistant strains. While the mechanism for how BAM functions remains elusive, previous structural studies have described each of the individual components of BAM, offering only a few clues to how the complex functions. Recently, a number of structures have been reported of complexes, including that of fully assembled BAM in differing conformational states. These studies have provided the molecular blueprint detailing the atomic interactions between the components and have revealed new details about BAM, which suggest a dynamic mechanism that may use conformational changes to assist in the biogenesis of new OMPs.
β-桶组装机器(BAM)是一种多组分复合物,负责革兰氏阴性菌中外膜β-桶蛋白(OMP)的生物合成,在线粒体和叶绿体中也存在保守系统。鉴于其在外膜完整性和表面暴露的毒力因子组装中的重要性,BAM是对抗病原菌,特别是多重耐药菌株的一个有吸引力的治疗靶点。虽然BAM发挥功能的机制仍不清楚,但先前的结构研究已经描述了BAM的各个组成部分,仅提供了关于该复合物如何发挥功能的一些线索。最近,已经报道了一些复合物的结构,包括处于不同构象状态的完全组装的BAM的结构。这些研究提供了详细说明各组分之间原子相互作用的分子蓝图,并揭示了关于BAM的新细节,这表明可能存在一种利用构象变化来协助新OMP生物合成的动态机制。