Streptococcus pneumoniae IgA1 protease: A metalloprotease that can catalyze in a split manner in vitro
Streptococcus pneumoniae IgA1 protease: A metalloprotease that can catalyze in a split manner in vitro
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DOI：
10.1002/pro.3110
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发表时间：
2017-03-01
期刊：
影响因子：
8
通讯作者：
Eisenmesser, Elan Z.
中科院分区：
文献类型：
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作者：
Chi, Ying-Chih;Rahkola, Jeremy T.;Eisenmesser, Elan Z.
来自不同致病菌的IgA1蛋白酶（IgA1P）特异性地在铰链区域切割人免疫球蛋白A1 (IgA1)，从而阻碍宿主的保护性免疫反应。肺炎链球菌（S. pneumoniae） IgA1P与丝氨酸或半胱氨酸类型的IgA1Ps或其他已知蛋白没有序列保守性，除了在金属蛋白酶中发现的保守的HExxH zn结合基序（1604-1608）。我们已经开发了一种新的表达系统来产生成熟的肺炎链球菌IgA1P，我们已经发现这种形式既附着在细菌细胞表面，又以完整的形式释放。我们的数据表明，肺炎链球菌IgA1P包含两个不同的区域，它们结合形成活性金属蛋白酶，这是第一个金属蛋白酶可以在体外分裂并重组形成活性酶的例子。通过利用这种新的结构域结构，我们发现肺炎链球菌IgA1P的n端区域包含IgA1的主要结合区域，尽管肺炎链球菌IgA1P的c端区域对于IgA1的裂解是必需的。我们的研究结果有助于深入了解肺炎链球菌IgA1P的蛋白质结构域结构和这一重要的肺炎链球菌感染毒力因子的功能。
IgA1 proteases (IgA1P) from diverse pathogenic bacteria specifically cleave human immunoglobulin A1 (IgA1) at the hinge region, thereby thwarting protective host immune responses. Streptococcus pneumoniae (S. pneumoniae) IgA1P shares no sequence conservation with serine or cysteine types of IgA1Ps or other known proteins, other than a conserved HExxH Zn-binding motif (1604-1608) found in metalloproteases. We have developed a novel expression system to produce the mature S. pneumoniae IgA1P and we have discovered that this form is both attached to the bacterial cell surface and released in its full form. Our data demonstrate that the S. pneumoniae IgA1P comprises two distinct regions that associate to form an active metalloprotease, the first such example of a metalloprotease that can be split in vitro and recombined to form an active enzyme. By capitalizing on this novel domain architecture, we show that the N-terminal region of S. pneumoniae IgA1P comprises the primary binding region for IgA1, although the C-terminal region of S. pneumoniae IgA1P is necessary for cleavage of IgA1. Our findings lend insight into the protein domain architecture of the S. pneumoniae IgA1P and function of this important virulence factor for S. pneumoniae infection.