MECHANISM OF ACTION OF THE GROUP-A STREPTOCOCCAL C5A INACTIVATOR
MECHANISM OF ACTION OF THE GROUP-A STREPTOCOCCAL C5A INACTIVATOR
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DOI：
10.1073/pnas.82.23.8144
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发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
CLEARY, PP
中科院分区：
文献类型：
--
作者：
WEXLER, DE;CHENOWETH, DE;CLEARY, PP
已发现A组强毒链球菌表达一种细胞表面因子，该因子具有灭活补体衍生的趋化因子的能力。为了确定该因子的作用机制，我们研究了纯化的失活剂与纯C5a趋化蛋白的相互作用。配体-受体结合研究表明，与天然C5a相比，链球菌趋化因子失活剂(SCFI)处理的C5a与多形核白细胞受体的结合能力显著降低。C5a的失活是通过一个非化学计量比和温度相关的过程发生的。NaDodSO4/PAGE分析表明，SCFI介导了C5adesArg分子量的小幅下降，而对灭活的C5a的羧基末端进行测序表明，C5a失去了一个六个残基的多肽。变性牛血清白蛋白在与SCFI长时间孵育后释放出不连续的多肽片段，这表明内切酶具有活性。虽然变性牛血清白蛋白没有被有效地切割，但天然牛血清白蛋白和其他天然蛋白对SCFI蛋白降解具有高度的抵抗力，这表明该活性具有自然界的特异性。
Virulent group A streptococci have been found to express a cell-surface factor that has the capability of inactivating complement-derived chemotatic factors. To determine the mechanism of action of this factor, we examined the interaction of purified inactivator with pure C5a chemotaxin. Ligand-receptor binding studies demonstrated that streptococcal chemotactic factor inactivator (SCFI)-treated C5a expressed a greatly reduced ability to bind to receptors of polymorphonuclear leukocytes as compared with native C5a. The inactivation of C5a occurred by a nonstoichiometric and temperature-dependent process. NaDodSO4/PAGE analysis indicated that SCFI mediated a small decrease in the molecular weight of C5adesArg, and sequencing of the carboxyl terminus of inactivated C5a demonstrated that a six-residue peptide was lost. The release of discrete peptide fragments from denatured bovine serum albumin upon prolonged incubation with SCFI was indicative of endoprotease activity. Although denatured bovine serum albumin was inefficiently cleaved, native bovine serum albumin and other native proteins were highly resistant to SCFI proteolysis; this indicated that activity was specific in nature.