A newly identified bacterial cell-penetrating peptide that reduces the transcription of pro-inflammatory cytokines
A newly identified bacterial cell-penetrating peptide that reduces the transcription of pro-inflammatory cytokines
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DOI：
10.1242/jcs.063016
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发表时间：
2010-07
影响因子：
4
通讯作者：
C. Rüter;Christoph Buss;J. Scharnert;G. Heusipp;M. A. Schmidt
中科院分区：
文献类型：
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作者：
C. Rüter;Christoph Buss;J. Scharnert;G. Heusipp;M. A. Schmidt
细胞渗透性蛋白，也称为细胞穿透肽（CPP），具有单独或与生物活性物质结合穿过细胞膜的能力。我们将耶尔森氏菌蛋白 YopM 鉴定为一种新型细菌细胞渗透性蛋白。在这里，我们描述了分离的重组 YopM 无需额外因子即可进入宿主细胞的能力。 YopM 的这种自主易位在多种细胞类型中得到证实，表明它是 YopM 的固有特性。使用 YopM 的截短版本，我们发现 YopM 的两个 N 末端 α 螺旋中的任何一个都介导易位到细胞中。此外，两个 α 螺旋还能够传递异源货物，例如 GFP 或 YopE。此外，我们发现，进入细胞后，YopM 发挥功能，有效下调促炎细胞因子（如肿瘤坏死因子-α 和白细胞介素 12、15 和 18）的转录。这一发现表明 YopM 作为蛋白质递送工具的潜在用途。此外，它可以在理解和评估 YopM 的细胞内和分子功能方面取得重要进展，而无需感染耶尔森氏菌。
Cell-permeable proteins, also called cell-penetrating peptides (CPPs), have the ability to cross cellular membranes, either alone or in association with bioactive cargo. We identified the Yersinia protein YopM as a novel bacterial cell-permeable protein. Here, we describe the ability of isolated recombinant YopM to enter host cells without a requirement for additional factors. This autonomous translocation of YopM was confirmed in several cell types, indicating that it is an intrinsic property of YopM. Using truncated versions of YopM, we show that either of the two N-terminal α-helices of YopM mediates translocation into the cells. Furthermore, the two α-helices are also able to deliver heterologous cargo, such as GFP or YopE. In addition, we found that, after entering the cells, YopM is functional and efficiently downregulates the transcription of pro-inflammatory cytokines (such as tumor necrosis factor-α and interleukins 12, 15 and 18). This finding suggests the potential use of YopM as a tool for protein delivery. Furthermore, it can lead to important advances in understanding and evaluating the intracellular and molecular function of YopM without the need for infection with Yersinia.