Kim Y U, Carroll M C, Isenman D E, Nonaka M, Pramoonjago P, Takeda J, Inoue K, Kinoshita T
Department of Bacteriology, Osaka University Medical School, Japan.
J Biol Chem. 1992 Feb 25;267(6):4171-6.
C5 convertase of the classical complement pathway is a protein complex consisting of C4b, C2a, and C3b. Within this complex C3b binds to C4b via an ester linkage. We now present evidence that the covalent C3b-binding site on human C4b is Ser at position 1217 of C4. We also show that formation of the covalently linked C4b.C3b complex occurs in the mouse complement system and that the C3b-binding site on mouse C4b is Ser at position 1213 which is homologous to Ser-1217 of human C4. Therefore, covalent binding of C3b to a single specific site on C4b within the classical pathway C5 convertase is likely a common phenomenon in the mammalian complement system. Specific noncovalent association of metastable C3b with C4b would occur first, leading to reaction of the thioester with a specific hydroxy group. This is supported by two lines of experimental evidence, one which shows that a mutant C4 that does not make a covalent linkage with C3b is still capable of forming C5 convertase and a second in which the C4b.C3b complex has been demonstrated by cross-linking erythrocytes bearing this C5 convertase.
经典补体途径的C5转化酶是一种由C4b、C2a和C3b组成的蛋白质复合物。在该复合物中，C3b通过酯键与C4b结合。我们现在提供证据表明，人C4b上的共价C3b结合位点是C4第1217位的丝氨酸。我们还表明，共价连接的C4b.C3b复合物在小鼠补体系统中形成，并且小鼠C4b上的C3b结合位点是第1213位的丝氨酸，与人C4的丝氨酸-1217同源。因此，在经典途径C5转化酶中，C3b与C4b上单个特定位点的共价结合可能是哺乳动物补体系统中的常见现象。亚稳态C3b与C4b的特异性非共价缔合将首先发生，导致硫酯与特定羟基反应。这得到了两条实验证据的支持，一条证据表明与C3b不形成共价连接的突变型C4仍能够形成C5转化酶，另一条证据是通过交联携带这种C5转化酶的红细胞证明了C4b.C3b复合物的存在。
