Institute for Molecular Bioscience, University of Queensland, Brisbane, Australia.
Institute of Microbiology and Infection, Birmingham, United Kingdom.
Elife. 2021 Feb 24;10:e63762. doi: 10.7554/eLife.63762.
Protein acylation is critical for many cellular functions across all domains of life. In bacteria, lipoproteins have important roles in virulence and are targets for the development of antimicrobials and vaccines. Bacterial lipoproteins are secreted from the cytosol via the Sec pathway and acylated on an N-terminal cysteine residue through the action of three enzymes. In Gram-negative bacteria, the Lol pathway transports lipoproteins to the outer membrane. Here, we demonstrate that the Aat secretion system is a composite system sharing similarity with elements of a type I secretion systems and the Lol pathway. During secretion, the AatD subunit acylates the substrate CexE on a highly conserved N-terminal glycine residue. Mutations disrupting glycine acylation interfere with membrane incorporation and trafficking. Our data reveal CexE as the first member of a new class of glycine-acylated lipoprotein, while Aat represents a new secretion system that displays the substrate lipoprotein on the cell surface.
蛋白质酰化对于所有生命领域的许多细胞功能都至关重要。在细菌中，脂蛋白在毒力中具有重要作用，并且是开发抗菌药物和疫苗的目标。细菌脂蛋白通过 Sec 途径从细胞质中分泌出来，并通过三种酶的作用在 N 端半胱氨酸残基上酰化。在革兰氏阴性菌中，Lol 途径将脂蛋白运输到外膜。在这里，我们证明 Aat 分泌系统是一个与 I 型分泌系统和 Lol 途径的元件具有相似性的复合系统。在分泌过程中，AatD 亚基在高度保守的 N 端甘氨酸残基上酰化底物 CexE。破坏甘氨酸酰化的突变会干扰膜的掺入和运输。我们的数据揭示了 CexE 作为第一个新的甘氨酸酰化脂蛋白的成员，而 Aat 则代表了一种新的分泌系统，它在细胞表面呈现底物脂蛋白。
