Crystal structure of chimeric antibody C2H7 Fab in complex with a CD20 peptide
文献类型：期刊论文
| 作者 | Du, JM; Wang, H; Zhong, C; Peng, BZ; Zhang, ML; Li, BH; Hou, S; Guo, YJ; Ding, JP |
| 刊名 | MOLECULAR IMMUNOLOGY
 |
| 出版日期 | 2008 |
| 卷号 | 45期号:10页码:2861-2868 |
| 关键词 | C2H7 CD20 epitope antibody structure |
| 通讯作者 | Guo, YJ (reprint author), Second Mil Med Univ, Int Joint Canc Inst, 800 Xiang Yin Rd, Shanghai 200433, Peoples R China.,yjguo@smmu.edu.cn |
| 英文摘要 | Anti-CD20 monoclonal antibodies have been proven to be efficient in the treatment of certain B-cell lymphomas and autoimmune diseases. Intriguingly, these antibodies seem to exert diverse functions with narrow epitope specificity. This study is to investigate the molecular basis of the fine specificity of 2H7 derived antibodies which are of great therapeutic potential. We show that chimeric 2H7 (C2H7) can mediate complement dependent cytotoxicity and antibody-dependent cellular cytotoxicity effects on CD20 positive human Burkitt lymphoma cells and the Fab fragment can well recognize and bind to an epitope peptide of the extracellular loop of CD20. The crystal structure of C2H7 in complex with the CD20 epitope peptide was determined at 2.6 angstrom resolution. The bound peptide displays a circular conformation and the binding specificity is mainly contributed by the (170)ANPS(173) motif and the disulfide bond of the peptide which maintains the unique conformation of the peptide. Compared with the complex structure of another anti-CD20 monoclonal antibody Rituximab with the same epitope peptide which was previously determined, the major differences lie in the CDR loop H3 of C2H7 which stretches outward against the interface. Correspondingly, the pocket which accommodates the peptide becomes wider and the peptide moves toward loop H3 and thus is more distant from loops H1 and H2. The hydrogen-bonding interactions are also quite different from those observed in the Rituximab-epitope peptide complex, and both the hydrophilic and hydrophobic interactions are less intense. Our data not only reveal the molecular basis for the fine specificity of C2H7 to CD20, but also provide valuable information for further improvement of antibodies derived from 2H7. (c) 2008 Elsevier Ltd. All rights reserved. |
| 学科主题 | Biochemistry & Molecular Biology ; Immunology |
| 类目[WOS] | Biochemistry & Molecular Biology ; Immunology |
| 关键词[WOS] | MONOCLONAL-ANTIBODIES ; FINE SPECIFICITY ; RITUXIMAB ; LYMPHOMAS ; EPITOPES ; CELLS ; MODEL |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000256318800016 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/1449]  |
| 专题 | 上海生化细胞研究所_上海生科院生化细胞研究所 |
| 推荐引用方式 GB/T 7714 | Du, JM,Wang, H,Zhong, C,et al. Crystal structure of chimeric antibody C2H7 Fab in complex with a CD20 peptide[J]. MOLECULAR IMMUNOLOGY,2008,45(10):2861-2868. |
| APA | Du, JM.,Wang, H.,Zhong, C.,Peng, BZ.,Zhang, ML.,...&Ding, JP.(2008).Crystal structure of chimeric antibody C2H7 Fab in complex with a CD20 peptide.MOLECULAR IMMUNOLOGY,45(10),2861-2868. |
| MLA | Du, JM,et al."Crystal structure of chimeric antibody C2H7 Fab in complex with a CD20 peptide".MOLECULAR IMMUNOLOGY 45.10(2008):2861-2868. |
入库方式： OAI收割
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。