Ghiso J, Saball E, Leoni J, Rostagno A, Frangione B
Department of Pathology, New York University Medical Center, NY 10016.
Proc Natl Acad Sci U S A. 1990 Feb;87(4):1288-91. doi: 10.1073/pnas.87.4.1288.
Hydropathic anticomplementarity of amino acids indicates that peptides derived from complementary DNA strands may form amphiphilic structures and bind one another. By using this concept, we have found that the antisense peptide Ser-Tyr-Asp-Leu complementary to the segment Gln-Ile-Val-Ala-Gly (residues 55-59) in cystatin C (an inhibitor of cysteine proteases) is located at positions 611-614 of the beta chain of human C4, the fourth component of complement. Here we describe and characterize the specific interaction between cystatin C and C4 by ligand affinity chromatography and ELISA. Interaction between the two native proteins was mimicked on replacement of one of them with the corresponding sense-antisense peptide coupled to a carrier protein, and the binding was inhibited by these synthetic peptides in solution. Through the interaction with C4, cystatin C may play a regulatory role in complement activation that might be of particular importance at tissue sites where both proteins are produced by macrophages.
氨基酸的亲水性抗互补性表明，源自互补DNA链的肽可能形成两亲结构并相互结合。利用这一概念，我们发现，与胱抑素C（一种半胱氨酸蛋白酶抑制剂）中Gln-Ile-Val-Ala-Gly片段（第55-59位氨基酸残基）互补的反义肽Ser-Tyr-Asp-Leu位于人补体第四成分C4的β链第611-614位。在此，我们通过配体亲和色谱法和酶联免疫吸附测定法描述并表征了胱抑素C与C4之间的特异性相互作用。当用与载体蛋白偶联的相应正义-反义肽取代其中一种天然蛋白时，模拟了两种天然蛋白之间的相互作用，并且溶液中的这些合成肽可抑制这种结合。通过与C4的相互作用，胱抑素C可能在补体激活中发挥调节作用，这在巨噬细胞同时产生这两种蛋白的组织部位可能尤为重要。
