Broad spectrum activity of a lectin-like bacterial serine protease family on human leukocytes.
Broad spectrum activity of a lectin-like bacterial serine protease family on human leukocytes.
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DOI：
10.1371/journal.pone.0107920
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Ruiz-Perez F
中科院分区：
文献类型：
--
作者：
Ayala-Lujan JL;Vijayakumar V;Gong M;Smith R;Santiago AE;Ruiz-Perez F
肠杆菌科的丝氨酸蛋白酶自转运蛋白（英语：serine protease autotransporter）有25种以上的蛋白酶，它们的功能明显不同，在系统发育上被分为两类，分别称为1和2。我们最近证明，由肠道和肠外致病性大肠杆菌产生的2类突变家族的两个成员Pic和Tsh能够在中性粒细胞和淋巴细胞上切割许多o糖基化蛋白，从而导致白细胞功能受损。在这里，我们发现2类的大多数成员具有凝集素样特性，并表现出依赖于糖蛋白类型和细胞谱系的不同蛋白酶活性。蛋白酶活性在几乎所有被检测的o糖基化蛋白中均可见，包括CD34、CD55、CD164、TIM1、TIM3、TIM4和C1-INH。我们还发现，尽管在粒细胞和单核细胞上，接连蛋白结合和切割糖蛋白的效率更高，但它们也能靶向B、T和自然杀伤淋巴细胞上的糖蛋白。最后，我们发现2类SPATEs的特征结构域-2不是糖蛋白酶活性所必需的，但SepA结构域-1中天然存在的残基在Pic结构域-1中的单个氨基酸突变足以阻碍糖蛋白酶活性。这项研究表明，大多数2类SPATEs具有冗余活性，并提示它们可能在免疫系统的多个水平上作为免疫调节剂起作用。
The serine protease autotransporter from Enterobacteriaceae (SPATE) family, which number more than 25 proteases with apparent diverse functions, have been phylogenetically divided into two distinct classes, designated 1 and 2. We recently demonstrated that Pic and Tsh, two members of the class-2 SPATE family produced by intestinal and extraintestinal pathogenic E. coli, were able to cleave a number of O-glycosylated proteins on neutrophils and lymphocytes resulting in impaired leukocyte functions. Here we show that most members of the class-2 SPATE family have lectin-like properties and exhibit differential protease activity reliant on glycoprotein type and cell lineage. Protease activity was seen in virtually all tested O-glycosylated proteins including CD34, CD55, CD164, TIM1, TIM3, TIM4 and C1-INH. We also show that although SPATE proteins bound and cleaved glycoproteins more efficiently on granulocytes and monocytes, they also targeted glycoproteins on B, T and natural killer lymphocytes. Finally, we found that the characteristic domain-2 of class-2 SPATEs is not required for glycoprotease activity, but single amino acid mutations in Pic domain-1 to those residues naturally occurring in domain-1 of SepA, were sufficient to hamper Pic glycoprotease activity. This study shows that most class-2 SPATEs have redundant activities and suggest that they may function as immunomodulators at several levels of the immune system.
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DOI：
10.1083/jcb.131.6.1623
发表时间：
1995-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bennett KL;Modrell B;Greenfield B;Bartolazzi A;Stamenkovic I;Peach R;Jackson DG;Spring F;Aruffo A
通讯作者：
Aruffo A
影响因子：
15.3
作者：
Otto, B R;van Dooren, S J;Nuijens, J H;Luirink, J;Oudega, B
通讯作者：
Oudega, B
影响因子：
3
作者：
Souza, Maria A.;Carvalho, Fernanda C.;Ruas, Luciana P.;Ricci-Azevedo, Rafael;Roque-Barreira, Maria Cristina
通讯作者：
Roque-Barreira, Maria Cristina
影响因子：
20.3
作者：
Laszik, Z;Jansen, PJ;Moore, KL
通讯作者：
Moore, KL
影响因子：
5.2
作者：
Clark MC;Baum LG
通讯作者：
Baum LG