FBXO2/SCF ubiquitin ligase complex directs xenophagy through recognizing bacterial surface glycan
FBXO2/SCF ubiquitin ligase complex directs xenophagy through recognizing bacterial surface glycan
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DOI：
10.15252/embr.202152584
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发表时间：
2021-09
期刊：
影响因子：
7.7
通讯作者：
Akihiro Yamada;Miyako Hikichi;T. Nozawa;I. Nakagawa
中科院分区：
文献类型：
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作者：
Akihiro Yamada;Miyako Hikichi;T. Nozawa;I. Nakagawa
嗜异性，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。虽然已知入侵的细菌被标记有泛素并被选择性地作为目标，但泛素连接酶如何识别入侵的细菌却知之甚少。在这里，我们表明FBXO 2是SKP 1/CUL 1/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，并促进泛素介导的对GAS的异噬作用。FBXO 2通过其糖结合基序和GAS表面上的GlcNAc表达靶向细胞溶质GAS。FBXO 2基因敲除后，细胞内GAS上泛素的积累和细菌的异嗜性降解减少。此外，SCF组分如SKP 1、CUL 1和ROC 1是泛素介导的针对GAS的异嗜性所必需的。因此，SCFFBXO 2识别GAS表面碳水化合物的GlcNAc残基，并在异种吞噬过程中的泛素化中发挥作用。
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, SCFFBXO2 recognizes GlcNAc residues of GAS surface carbohydrates and functions in ubiquitination during xenophagy.