Section Molecular Microbiology, Department of Molecular Cell Biology, Amsterdam Institute for Molecules, Medicines and Systems (AIMMS), Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.
Abera Bioscience AB, SE-111 45 Stockholm, Sweden.
FEMS Microbiol Lett. 2018 Sep 1;365(18). doi: 10.1093/femsle/fny165.
The classical monomeric autotransporters are ubiquitously used by Gram-negative bacteria to export virulence and colonization factors to their cell surface or into their surroundings. They are expressed as monomeric proteins that pass the inner and outer membrane in two consecutive steps facilitated by the Sec translocon and the Bam complex, respectively. In this mini-review we discuss how autotransporters translocate their secreted functional domains across the outer membrane. We highlight the interactions with the Bam complex and discuss how specific features of the recently solved structure of Bam lead to a mechanistic model for autotransporter secretion. Furthermore, the autotransporter secretion pathway is the system of choice for surface display of heterologous proteins for biotechnical and biomedical purposes. We summarize recent advances in the application of autotransporters with a focus on outer membrane vesicle vaccine development and discuss its limitations in secreting more complex heterologous proteins. Finally, we present an exciting new technology to circumvent secretion limitations by ligating heterologous proteins of interest to autotransporters that are displayed on the cell surface.
经典的单体型自转运蛋白被革兰氏阴性菌广泛用于将毒力因子和定植因子输出到细胞表面或周围环境中。它们作为单体蛋白表达,通过 Sec 转运体和 Bam 复合物分别在两个连续的步骤中穿过内膜和外膜。在这篇迷你综述中,我们讨论了自转运蛋白如何将其分泌的功能域穿过外膜转运。我们强调了与 Bam 复合物的相互作用,并讨论了最近解决的 Bam 结构的特定特征如何导致自转运蛋白分泌的机制模型。此外,自转运蛋白分泌途径是用于生物技术和生物医学目的的异源蛋白表面展示的首选系统。我们总结了自转运蛋白应用的最新进展,重点介绍了外膜囊泡疫苗的开发,并讨论了其在分泌更复杂的异源蛋白方面的局限性。最后,我们提出了一种令人兴奋的新技术,通过将感兴趣的异源蛋白与在细胞表面展示的自转运蛋白连接来规避分泌限制。