Molecular cloning and characterization of two Helicobacter pylori genes coding for plasminogen-binding proteins
Molecular cloning and characterization of two Helicobacter pylori genes coding for plasminogen-binding proteins
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DOI：
10.1073/pnas.0307329101
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发表时间：
2004-02-17
影响因子：
11.1
通讯作者：
Kronvall, G
中科院分区：
文献类型：
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作者：
Jönsson, K;Guo, BP;Kronvall, G
幽门螺杆菌结合许多宿主细胞蛋白，包括血浆蛋白纤溶酶原，它是丝氨酸蛋白酶纤溶酶的前酶。两种幽门螺杆菌纤溶酶原结合蛋白已被描述；然而，没有基因被鉴定出来。本研究利用噬菌体展示文库从幽门螺杆菌CCUG 17874基因组中克隆了介导与纤溶酶原结合的两个基因。其中1个基因与H. pylori 26695 HP0508同源性为96.6%。随后的数据库检索显示，HP0508富含赖氨酸的C端片段的氨基酸序列与HP0863的C端相同。从HP0508和HP0863中表达的重组蛋白以赖氨酸依赖的方式特异性结合纤溶酶原。我们将这两个基因分别命名为pgbA和pgbB。这些蛋白在各种幽门螺杆菌菌株中表达，具有表面暴露的结构域，并且不抑制纤溶酶原的激活。这些结果表明，pgbA和pgbB可能使幽门螺杆菌在其表面包裹纤溶酶原，随后被激活为纤溶酶。蛋白酶活性的表面获取可能会增强幽门螺杆菌的毒力。
Helicobacter pylori binds a number of host cell proteins, including the plasma protein plasminogen, which is the proenzyme of the serine protease plasmin. Two H. pylori plasminogen-binding proteins have been described; however, no genes were identified. Here we report the use of a phage display library to clone two genes from the H. pylori CCUG 17874 genome that mediate binding to plasminogen. DNA sequence analysis of one of these genes revealed 96.6% homology with H. pylori 26695 HP0508. A subsequent database search revealed that the amino acid sequence of a lysine-rich C-terminal segment of HP0508 is identical to the C terminus of HP0863. Recombinant proteins expressed from HP0508 and HP0863 bound plasminogen specifically and in a lysine-dependent manner. We designate these genes pgbA and pgbB, respectively. These proteins are expressed by a variety of H. pylori strains, have surface-exposed domains, and do not inhibit plasminogen activation. These results indicate that pgbA and pgbB may allow H. pylori to coat its exterior with plasminogen, which subsequently can be activated to plasmin. The surface acquisition of protease activity may enhance the virulence of H. pylori.