Active site of C3a anaphylatoxin: contributions of the lipophilic and orienting residues.
Active site of C3a anaphylatoxin: contributions of the lipophilic and orienting residues.
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C3a 过敏毒素的活性位点：亲脂性和定向残基的贡献。
DOI：
10.1021/bi00299a001
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发表时间：
1984
期刊：
影响因子：
2.9
通讯作者：
Hugli,TE
中科院分区：
文献类型：
--
作者：
Unson,CG;Erickson,BW;Hugli,TE
Cecilia G.Unson，Bruce W.Erickson，*和Tony E.Hugli摘要：血清补体级联的激活会产生C3a过敏毒素，它是炎症的主要介质。C3a羧基末端的活性部位五肽Leu-Gly-Leu-Ala-Arg(73-77个残基)显示了天然77个残基多肽的炎症活性和特异性。通过测试22个合成的五肽类似物对豚鼠回肠肌条的收缩能力，以及对人C3a或C5a引起的收缩的脱敏作用，研究了该活性部位的重要功能特征。肥大细胞和嗜碱性粒细胞上的C3a受体可能含有亲脂性基团。人血清补体系统的激活导致补体第三组分C3裂解成活化肽C3a(8900)和活化蛋白C3b(MR 171000)(Hugli&Miiller-Eberhard，1978年)。C3b与免疫复合物或细胞表面等受体表面的共价结合是通过其亚稳态结合部位发生的，该结合部位可能包含一个反应性的15元硫代内酯环(Tack等人，1980；Khan和Erickson，1981,1982)。边界C3b能刺激细胞和免疫复合体的吞噬功能，并在补体蛋白C3和C5的激活过程中发挥重要作用。
Cecilia G. Unson, Bruce W. Erickson,* and Tony E. Hugli abstract: Activation of the serum complement cascade generates C3a anaphylatoxin, a primary mediator of inflammation. The active-site pentapeptide from the COOH ter-minus of C3a, Leu-Gly-Leu-Ala-Arg (residues 73-77), exhibits the inflammatory activities and specificity of the native 77-residue polypeptide. Functionally important features of this active site were studied by testing the ability of 22 synthetic analogues of this pentapeptide to contract isolated muscle strips from guinea pig ileum and to desensitize this tissue to con-traction induced by human C3a or C5a. The C3a receptors on mast cells and basophils probably contain lipophilic groups.^^. ctivation of the complement system of human serum re-sults in cleavage of C3, the third complement component, into the activation peptide C3a {8900) and the activated protein C3b (Mr 171000)(Hugli & Miiller-Eberhard, 1978). Co-valent attachment of C3b to receptive surfaces (Law et al., 1979) such as immune complexes or cell surfaces occurs through its metastable binding site, whichmight contain a reactive 15-membered thiolactone ring (Tack et al., 1980; Khan & Erickson, 1981, 1982). BoundC3b stimulates the phagocytosis of cells and immune complexes and plays an essential role in activation of the complement proteins C3 and C5.