Release of protein A from the cell wall of Staphylococcus aureus
Release of protein A from the cell wall of Staphylococcus aureus
复制标题
DOI：
10.1073/pnas.1317181111
复制
发表时间：
2014-01-28
影响因子：
11.1
通讯作者：
Missiakas, Dominique
中科院分区：
文献类型：
--
作者：
Becker, Samuel;Frankel, Matthew B.;Missiakas, Dominique
金黄色葡萄球菌蛋白A(SPA)通过结合其C端LPXTG基序的苏氨酰基(T)和肽聚糖交叉桥(即Gly(5))而被锚定在金黄色葡萄球菌的细胞壁被膜上。SPA结合免疫球蛋白的Fc伽马域，保护葡萄球菌免受吞噬细胞的清除。此外，SpA使B细胞受体交叉连接，以改变宿主的适应性免疫反应。SpA从细菌表面释放进入宿主免疫系统的机制尚不清楚。在这里，我们证明了SpA是通过与其C端苏氨酸连接的四肽-四甘醇[L-丙氨酸-D-iGln-(SpA-Gly(5))L-赖氨酸-D-丙氨酸-甘氨酸(4)]来释放的。LytN是一种跨壁毛脲水解酶，它通过从附着的肽聚糖中去除氨基糖[即N-乙酰胞壁酸-N-乙酰氨基葡萄糖(MurNAc-GlcNAc)]来促进SpA的释放，而LytM是一种五甘基环内肽酶，可以触发细菌被膜上的多肽释放。提出了一个模型，在该模型中，murein水解酶裂解释放的spA的锚结构，以改变宿主的免疫反应。
Staphylococcal protein A (SpA) is anchored to the cell wall envelope of Staphylococcus aureus by sortase A, which links the threonyl (T) of its C-terminal LPXTG motif to peptidoglycan cross-bridges (i.e., Gly(5)). SpA binds the Fc gamma domains of IgG and protects staphylococci from opsonophagocytic clearance. Moreover, SpA cross-links B-cell receptors to modify host adaptive immune responses. The mechanisms whereby SpA is released from the bacterial surface to access the host's immune system are not known. Here we demonstrate that SpA is released with murein tetrapeptide-tetraglycyl [L-Ala-D-iGln-(SpA-Gly(5))L-Lys-D-Ala-Gly(4)] linked to its C-terminal threonyl. LytN, a cross-wall murein hydrolase, contributes to the release of SpA by removing amino sugars [i.e., N-acetylmuramic acid-N-acetyl-glucosamine (MurNAc-GlcNAc)] from attached peptidoglycan, whereas LytM, a pentaglycyl-endopeptidase, triggers polypeptide release from the bacterial envelope. A model is proposed whereby murein hydrolases cleave the anchor structure of released SpA to modify host immune responses.