Bokisch V A, Dierich M P, Mūller-Eberhard H J
Proc Natl Acad Sci U S A. 1975 Jun;72(6):1989-93. doi: 10.1073/pnas.72.6.1989.
The third component of complement (C3) fulfills a pivotal role in the functions of the complement system. We have investigated the topological relationships among its polypeptide chains, physiologic fragments, enzyme attack regions, and functional sites. C3 consists of two chains (alpha and beta) which are linked by disulfide bonds and noncovalent forces and which have molecular weights of, respectively, 120,000 and 75,000. C3 is activated by action of C3 convertase on the alpha-chain. With hydrolysis of one polypeptide bonds, C3a, the 9000 dalton activation peptide is dislocated from the NH2-terminal portion of the alpha-chain. A previously concealed binding region is thereby transiently revealed in the C3b-fragment (181,000 dalton) which displays affinity for apparently nonspecific acceptors present on biological membranes. Binding of nascent C3b membranes occurs through the C3d portion of the fragment because subsequent action of the C3b-inactivator or trypsin on bound C3b causes release of C3c, but not of C3d. Bound C3b and C3d possess stable sites that are capable of binding to specific receptors present on a limited variety of cells. We propose that all known physiologically occurring fragments of C3 arise by enzymatic cleavage of the alpha-chain: C3a, C3b, C3c, and C3d. Whereas C3a (alpha1) and C3e (alpha2) consist of a single chain and C3b consists of two chains (alpha' and beta), C3c is composed of the entire beta-chain and multiple fragments of the alpha-chain, each of which is linked by disulfide bonds to the beta-chain.
补体系统的第三个成分（C3）在补体系统功能中起关键作用。我们研究了其多肽链、生理片段、酶攻击区域和功能位点之间的拓扑关系。C3由两条链（α链和β链）组成，它们通过二硫键和非共价力相连，分子量分别为120,000和75,000。C3通过C3转化酶对α链的作用而被激活。随着一个多肽键的水解，9000道尔顿的激活肽C3a从α链的氨基末端部分脱离。由此，一个先前隐藏的结合区域在C3b片段（181,000道尔顿）中短暂暴露，该片段对生物膜上明显非特异性的受体具有亲和力。新生的C3b与膜的结合通过片段的C3d部分发生，因为C3b灭活剂或胰蛋白酶对结合的C3b的后续作用会导致C3c释放，但不会导致C3d释放。结合的C3b和C3d具有能够与有限种类细胞上存在的特异性受体结合的稳定位点。我们提出，所有已知的C3生理片段都是由α链的酶促裂解产生的：C3a、C3b、C3c和C3d。其中C3a（α1）和C3e（α2）由单链组成，C3b由两条链（α'和β）组成，C3c由整个β链和α链的多个片段组成，每个片段都通过二硫键与β链相连。
