The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway.
The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway.
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DOI：
10.1016/j.molcel.2018.01.029
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发表时间：
2018-02-15
期刊：
影响因子：
16
通讯作者：
Veillard F
中科院分区：
文献类型：
--
作者：
Issa N;Guillaumot N;Lauret E;Matt N;Schaeffer-Reiss C;Van Dorsselaer A;Reichhart JM;Veillard F
微生物或内源性分子模式以及病原体功能特征可以激活先天免疫系统。尽管通过模式识别受体检测感染已经进行了详细的研究，但对毒力因子活动的感知仍然较少。在果蝇中，遗传证据表明，丝氨酸蛋白酶Persephone属于由异常蛋白水解活性激活诱导Toll信号通路的危险途径。然而，该通路的激活机制及其特异性都尚未确定。在这里，我们在珀尔塞福涅的前结构域中发现了一个独特的区域，该区域作为外源蛋白酶的诱饵，独立于它们的来源、类型或特异性。这个诱饵区域的切割构成了序列激活的第一步，并将珀尔塞福涅随后的成熟许可给内源性半胱氨酸组织蛋白酶26-29-p。我们的研究结果表明，珀尔塞福涅本身是一种免疫受体，能够通过毒力因子活动而不是分子模式来感知广泛的微生物。所有病原体分泌的蛋白酶都激活Toll通路的危险感应部分，蛋白酶珀尔塞福涅是微生物蛋白水解活性的免疫传感器，珀尔塞福涅酶原中的一个敏感区域作为外源蛋白酶的诱饵，诱饵区域的水解启动了宿主组织蛋白酶对珀尔塞福涅的成熟26-29-p。Issa等人表明，果蝇Toll通路通过位于Persephone前结构域的水解敏感区域感知病原体蛋白酶。这个诱饵区域的分裂启动了珀尔塞福涅的成熟和宿主组织蛋白酶26-29-p激活的途径。
Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns. All pathogen-secreted proteases activate the danger-sensing arm of the Toll pathway The protease Persephone is the immune sensor for microbial proteolytic activities A sensitive region in Persephone zymogen functions as a bait for exogenous proteases Bait-region hydrolysis primes maturation of Persephone by the host cathepsin 26-29-p Innate immune systems are activated by microbial molecular patterns or pathogen functional features. Issa et al. show that the Drosophila Toll pathway senses pathogen proteases through a hydrolysis-sensitive region localized in the Persephone pro-domain. Cleavage of this bait region primes maturation of Persephone and activation of the pathway by the host cathepsin 26-29-p.
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影响因子：
64.8
作者：
Cheng, Zhenyu;Li, Jian-Feng;Niu, Yajie;Zhang, Xue-Cheng;Woody, Owen Z.;Xiong, Yan;Djonovic, Slavica;Millet, Yves;Bush, Jenifer;McConkey, Brendan J.;Sheen, Jen;Ausubel, Frederick M.
通讯作者：
Ausubel, Frederick M.
DOI：
10.1007/978-3-319-46503-6_6
发表时间：
2017-01-01
期刊：
MACROMOLECULAR PROTEIN COMPLEXES: STRUCTURE AND FUNCTION
影响因子：
--
作者：
Garcia-Ferrer, Irene;Marrero, Aniebrys;Goulas, Theodoros
通讯作者：
Goulas, Theodoros
影响因子：
64.5
作者：
通讯作者：
--
DOI：
10.1073/pnas.070357597
发表时间：
2000-03-28
影响因子：
11.1
作者：
Basset, A;Khush, RS;Lemaitre, B
通讯作者：
Lemaitre, B
影响因子：
5
作者：
Caughey GH
通讯作者：
Caughey GH