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Analysis of the specificity of bacterial immunoglobulin A (IgA) proteases by a comparative study of ape serum IgAs as substrates.

机译:通过对猿血清IgAs作为底物的比较研究来分析细菌免疫球蛋白A(IgA)蛋白酶的特异性。

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Immunoglobulin A (IgA) proteases are bacterial enzymes with substrate specificity for human serum and secretory IgAs. To further define the basis of this specificity, we examined the ability of IgA proteases of Clostridium ramosum, Streptococcus pneumoniae (EC 3.4.24.13), Neisseria meningitidis (EC 3.4.21.72), and Haemophilus influenzae (EC 3.4.21.72) to cleave serum IgAs of gorillas, chimpanzees, and orangutans. All enzymes cleaved the IgAs of the three apes despite differences in ape IgA1 hinge sequence relative to the human prototype. To directly compare the ape and human hinge cleavage sites, the sites were identified in eight ape IgA digests. This analysis confirmed that ape proteins were all cleaved in the IgA hinge region, in all but one case after proline residues. The exception, C. ramosum protease, cleaved gorilla and chimpanzee IgAs at peptide bonds having no proline, but the scissile bonds were in the same hinge location as the Pro-221-Val-222 cleaved in human IgA1. These data indicate that proline is not an invariant substrate requirement for all IgA proteases and that the location of the scissile bond, in addition to its composition, is a critical determinant of cleavage specificity.
机译:免疫球蛋白A(IgA)蛋白酶是对人血清和分泌型IgA具有底物特异性的细菌酶。为了进一步确定这种特异性的基础,我们研究了鼠李氏梭菌,肺炎链球菌(EC 3.4.24.13),脑膜炎奈瑟氏球菌(EC 3.4.21.72)和流感嗜血杆菌(EC 3.4.21.72)的IgA蛋白酶裂解血清的能力。大猩猩,黑猩猩和猩猩的IgA。尽管猿类IgA1铰链序列相对于人类原型存在差异,但所有酶均切割了三种猿类的IgA。为了直接比较猿和人类铰链的裂解位点,在八种猿IgA消化物中鉴定了这些位点。该分析证实,在脯氨酸残基之后的除了一种情况以外的所有情况下,猿蛋白都在IgA铰链区被切割。例外,C。ramosum蛋白酶在没有脯氨酸的肽键处切割了大猩猩和黑猩猩IgAs,但易裂键与在人IgA1中切割的Pro-221-Val-222位于相同的铰链位置。这些数据表明脯氨酸不是所有IgA蛋白酶的不变底物要求,并且易裂键的位置(除了其组成之外)是裂解特异性的关键决定因素。

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