Quantitative Visualization of the Interaction between Complement Component C1 and Immunoglobulin G: The Effect of CH1 Domain Deletion

International Journal of Molecular Sciences

Hiroki Watanabe¹  Saeko Yanaka¹  Rina Yogo¹  Jiana Shen¹  Koichi Kato¹  Takayuki Uchihashi¹  Shigetaka Nishiguchi¹  Hirokazu Yagi² 

[1] Exploratory Research Center on Life and Living Systems (ExCELLS), Institute for Molecular Science (IMS), National Institutes of Natural Sciences, 5-1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan;Faculty and Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan;

关键词: immunoglobulin G;    complement component C1;    high-speed atomic force microscopy;    C_H1;    C_L;   

DOI  :  10.3390/ijms23042090

来源: DOAJ

【 摘 要 】

Immunoglobulin G (IgG) adopts a modular multidomain structure that mediates antigen recognition and effector functions, such as complement-dependent cytotoxicity. IgG molecules are self-assembled into a hexameric ring on antigen-containing membranes, recruiting the complement component C1q. In order to provide deeper insights into the initial step of the complement pathway, we report a high-speed atomic force microscopy study for the quantitative visualization of the interaction between mouse IgG and the C1 complex composed of C1q, C1r, and C1s. The results showed that the C1q in the C1 complex is restricted regarding internal motion, and that it has a stronger binding affinity for on-membrane IgG2b assemblages than C1q alone, presumably because of the lower conformational entropy loss upon binding. Furthermore, we visualized a 1:1 stoichiometric interaction between C1/C1q and an IgG2a variant that lacks the entire C_H1 domain in the absence of an antigen. In addition to the canonical C1q-binding site on Fc, their interactions are mediated through a secondary site on the C_L domain that is cryptic in the presence of the C_H1 domain. Our findings offer clues for novel-modality therapeutic antibodies.

【 授权许可】

Unknown