BamA功能需要侧向开口和出口孔的形成。
Lateral opening and exit pore formation are required for BamA function.
作者信息
Noinaj Nicholas, Kuszak Adam J, Balusek Curtis, Gumbart James C, Buchanan Susan K
机构信息
Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
School of Physics, Georgia Institute of Technology, Atlanta, GA 30332, USA.
出版信息
Structure. 2014 Jul 8;22(7):1055-62. doi: 10.1016/j.str.2014.05.008. Epub 2014 Jun 26.
The outer membrane of Gram-negative bacteria is replete with a host of β-barrel outer membrane proteins (OMPs). Despite serving a variety of essential functions, including immune response evasion, the exact mechanism of OMP folding and membrane insertion remains largely unclear. The β-barrel assembly machinery complex is required for OMP biogenesis. Crystal structures and molecular dynamics (MD) simulations of the central and essential component, BamA, suggest a mechanism involving lateral opening of its barrel domain. MD simulations reported here reveal an additional feature of BamA: a substrate exit pore positioned above the lateral opening site. Disulfide crosslinks that prevent lateral opening and exit pore formation result in a loss of BamA function, which can be fully rescued by the reductant tris(2-carboxyethyl)phosphine. These data provide strong evidence that lateral opening and exit pore formation are required for BamA function.
革兰氏阴性菌的外膜富含大量β桶状外膜蛋白（OMP）。尽管OMP发挥着多种重要功能，包括逃避免疫反应，但其折叠和插入膜的确切机制仍不清楚。β桶组装机器复合体是OMP生物合成所必需的。核心且关键的组分BamA的晶体结构和分子动力学（MD）模拟表明，其机制涉及桶状结构域的侧向打开。本文报道的MD模拟揭示了BamA的另一个特征：在侧向开口位点上方有一个底物出口孔。阻止侧向打开和出口孔形成的二硫键交联会导致BamA功能丧失，而还原剂三（2-羧乙基）膦可完全挽救该功能丧失。这些数据提供了有力证据，表明侧向打开和出口孔形成是BamA发挥功能所必需的。
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