Xenophagy, also known as antibacterial selective autophagy, degrades invading bacterial pathogens such as group A Streptococcus (GAS) to defend cells. Although invading bacteria are known to be marked with ubiquitin and selectively targeted by xenophagy, how ubiquitin ligases recognize invading bacteria is poorly understood. Here, we show that FBXO2, a glycoprotein-specific receptor for substrate in the SKP1/CUL1/F-box protein (SCF) ubiquitin ligase complex, mediates recognition of GlcNAc side chains of the GAS surface carbohydrate structure and promotes ubiquitin-mediated xenophagy against GAS. FBXO2 targets cytosolic GAS through its sugar-binding motif and GlcNAc expression on the GAS surface. FBXO2 knockout resulted in decreased ubiquitin accumulation on intracellular GAS and xenophagic degradation of bacteria. Furthermore, SCF components such as SKP1, CUL1, and ROC1 are required for ubiquitin-mediated xenophagy against GAS. Thus, SCF^FBXO2 recognizes GlcNAc residues of GAS surface carbohydrates and functions in ubiquitination during xenophagy.

中文翻译：

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FBXO2/SCF 泛素连接酶复合物通过识别细菌表面聚糖指导异种吞噬

Xenophagy，也称为抗菌选择性自噬，降解入侵的细菌病原体如 A 组链球菌(GAS) 以保护细胞。尽管已知入侵细菌被泛素标记并被异体吞噬选择性地靶向，但泛素连接酶如何识别入侵细菌却知之甚少。在这里，我们展示了 FBXO2，SKP1/CUL1/F-box 蛋白 (SCF) 泛素连接酶复合物中底物的糖蛋白特异性受体，介导对 GAS 表面碳水化合物结构的 GlcNAc 侧链的识别，并促进泛素介导的针对气体。FBXO2通过其糖结合基序和GAS表面上的GlcNAc表达靶向胞质GAS。FBXO2敲除导致泛素在细胞内 GAS 上的积累减少和细菌的异食性降解。此外，SCF 成分如 SKP1、CUL1 和 ROC1 是泛素介导的针对 GAS 的异体吞噬所必需的。因此，SCF ^FBXO2可识别 GAS 表面碳水化合物的 GlcNAc 残基，并在异种吞噬过程中发挥泛素化作用。