Kojouharova Mihaela S, Tsacheva Ivanka G, Tchorbadjieva Magdalena I, Reid Kenneth B M, Kishore Uday
Department of Biochemistry, Sofia University, St. Kliment Ohridski, 8 Dragan Tzankov Str, Sofia 1164, Bulgaria.
Biochim Biophys Acta. 2003 Nov 3;1652(1):64-74. doi: 10.1016/j.bbapap.2003.08.003.
As a charge pattern recognition molecule, human C1q can bind a range of immunoglobulin and non-immunoglobulin ligands via its carboxy-terminal globular domain and activate the classical complement pathway. Each globular domain has a heterotrimeric organization, composed of the carboxy-terminal halves of one A (ghA), one B (ghB), and one C (ghC) chain. Recently, we have found that the recombinant forms of individual ghA, ghB and ghC bind differentially to IgG, IgM, gp41 peptide 601-613 of human immunodeficiency virus-1 (HIV-1), gp21 peptide 400-429 of human T cell lymphotrophic virus-I (HTLV-I), beta-amyloid peptide, and apoptotic cells, suggesting a modular organization of the globular domain. This paper examines the interaction of ghA, ghB and ghC with two known C1q ligands: Klebsiella pneumoniae porin OmpK36 and salivary agglutinin. In addition, we have used a panel of recombinant single-chain antibodies (scFv) specific for ghA, ghB and ghC in order to map sites on the heterotrimeric globular domain which are likely to interact with IgG1, IgG3, IgM, OmpK36, salivary agglutinin and gp41 loop peptide. The combined use of recombinant ghA, ghB, ghC and single-chain antibodies has revealed at least three ligand-binding sites on the globular domain of C1q: one is IgG- and OmpK36-specific, the second (IgM-binding site) is most likely overlapping with IgG/OmpK36 binding site, and the third (the gp41-binding site) seems to be located at the junction between the collagen and globular domains.
作为一种电荷模式识别分子，人C1q可通过其羧基末端球状结构域结合一系列免疫球蛋白和非免疫球蛋白配体，并激活经典补体途径。每个球状结构域具有异源三聚体结构，由一条A链（ghA）、一条B链（ghB）和一条C链（ghC）的羧基末端半段组成。最近，我们发现单个ghA、ghB和ghC的重组形式与IgG、IgM、人类免疫缺陷病毒1型（HIV-1）的gp41肽601-613、人类嗜T细胞病毒I型（HTLV-I）的gp21肽400-429、β-淀粉样肽及凋亡细胞的结合存在差异，提示球状结构域具有模块化组织。本文研究了ghA、ghB和ghC与两种已知的C1q配体：肺炎克雷伯菌孔蛋白OmpK36和唾液凝集素的相互作用。此外，我们使用了一组对ghA、ghB和ghC具有特异性的重组单链抗体（scFv），以绘制异源三聚体球状结构域上可能与IgG1、IgG3、IgM、OmpK36、唾液凝集素和gp41环肽相互作用的位点。重组ghA、ghB、ghC和单链抗体的联合使用揭示了C1q球状结构域上至少三个配体结合位点：一个是IgG和OmpK36特异性的，第二个（IgM结合位点）很可能与IgG/OmpK36结合位点重叠，第三个（gp41结合位点）似乎位于胶原结构域和球状结构域的交界处。
