Two Amphioxus ApeC-Containing Proteins Bind to Microbes and Inhibit the TRAF6 Pathway.
Two Amphioxus ApeC-Containing Proteins Bind to Microbes and Inhibit the TRAF6 Pathway.
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两种文昌鱼 ApeC 蛋白与微生物结合并抑制 TRAF6 通路
DOI：
10.3389/fimmu.2021.715245
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发表时间：
2021
影响因子：
7.3
通讯作者：
Huang S
中科院分区：
文献类型：
--
作者：
Li J;Li Y;Fan Z;Chen S;Yan X;Yue Z;Huang G;Liu S;Zhang H;Chen S;Dong M;Xu A;Huang S
apextrin C 末端 (ApeC) 结构域是一类新发现的蛋白质结构域，其起源可以追溯到原核生物。含 ApeC 的蛋白质 (ACP) 已在多种海洋和水生无脊椎动物中发现，但其功能和潜在机制在很大程度上尚不清楚。早期研究表明文昌鱼 ACP1 和 ACP2 与细菌细胞壁结合并在免疫中发挥作用。在这里，我们鉴定了另外两个文昌鱼 ACP（ACP3 和 ACP5），它们与 ACP1/2 属于同一系统发育分支，但表现出不同的表达模式和序列分歧（40-50% 序列同一性）。 ACP3和ACP5均主要在肠和肝盲肠中表达，并且在细菌攻击后均可上调。原核表达的重组ACP3和ACP5均可与多种细菌和酵母结合，表现出凝集活性，但无杀菌活性。 ELISA 测定表明，它们的 ApeC 结构域可以与肽聚糖 (PGN) 相互作用，但不能与脂磷壁酸 (LTA)、脂多糖 (LPS) 和酵母聚糖 A 相互作用。此外，它们只能与金黄色葡萄球菌的 Lys 型 PGN 结合，但不能与枯草芽孢杆菌的 DAP 型 PGN 结合，也不能与 PGN 的部分（例如 MDP、NAM 和 MDP）结合。 NAG。该识别谱与ACP1/2的识别谱不同。我们还发现，当在哺乳动物细胞中表达时，ACP3 可以通过保守的非 ApeC 区域与 TRAF6 相互作用，从而抑制 TRAF6 的泛素化，从而抑制下游 NF-κB 的激活。这项工作帮助定义了 ACP 的一个新亚家族，该亚家族具有保守的结构，并具有相关但多样化的分子功能。其成员具有双重作用，ApeC 作为凝集素，保守的未知区域作为信号转导调节剂。这些发现扩展了我们对 ACP 功能的理解，并可能指导未来 ACP 在不同动物进化枝中的作用的研究。
The apextrin C-terminal (ApeC) domain is a class of newly discovered protein domains with an origin dating back to prokaryotes. ApeC-containing proteins (ACPs) have been found in various marine and aquatic invertebrates, but their functions and the underlying mechanisms are largely unknown. Early studies suggested that amphioxus ACP1 and ACP2 bind to bacterial cell walls and have a role in immunity. Here we identified another two amphioxus ACPs (ACP3 and ACP5), which belong to the same phylogenetic clade with ACP1/2, but show distinct expression patterns and sequence divergence (40-50% sequence identities). Both ACP3 and ACP5 were mainly expressed in the intestine and hepatic cecum, and could be up-regulated after bacterial challenge. Both prokaryotic-expressed recombinant ACP3 and ACP5 could bind with several species of bacteria and yeasts, showing agglutinating activity but no microbicidal activity. ELISA assays suggested that their ApeC domains could interact with peptidoglycan (PGN), but not with lipoteichoic acid (LTA), lipopolysaccharides (LPS) and zymosan A. Furthermore, they can only bind to Lys-type PGN from Staphylococcus aureus, but not to DAP-type PGN from Bacillus subtilis and not to moieties of PGN such as MDPs, NAMs and NAGs. This recognition spectrum is different from that of ACP1/2. We also found that when expressed in mammalian cells, ACP3 could interact with TRAF6 via a conserved non-ApeC region, which inhibited the ubiquitination of TRAF6 and hence suppressed downstream NF-κB activation. This work helped define a novel subfamily of ACPs, which have conserved structures, and have related yet diversified molecular functions. Its members have dual roles, with ApeC as a lectin and a conserved unknown region as a signal transduction regulator. These findings expand our understanding of the ACP functions and may guide future research on the role of ACPs in different animal clades.
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影响因子：
4
作者：
Louis A;Roest Crollius H;Robinson-Rechavi M
通讯作者：
Robinson-Rechavi M
DOI：
10.1093/bioinformatics/8.3.275
发表时间：
1992-06-01
期刊：
COMPUTER APPLICATIONS IN THE BIOSCIENCES
影响因子：
--
作者：
JONES, DT;TAYLOR, WR;THORNTON, JM
通讯作者：
THORNTON, JM
含 ApeC 的蛋白质分布广泛、多样性高且起源古老
影响因子：
4.1
作者：
Li, Yuhui;Li, Jin;Huang, Shengfeng
通讯作者：
Huang, Shengfeng
影响因子：
4.7
作者：
McDowell, Ian C.;Modak, Tejashree H.;Gomez-Chiarri, Marta
通讯作者：
Gomez-Chiarri, Marta
影响因子：
2.9
作者：
Huang, Gonghua;Liu, Hui;Xu, Anlong
通讯作者：
Xu, Anlong