Structural basis for recognition of CD20 by therapeutic antibody rituximab
文献类型:期刊论文
作者 | Du, JM; Wang, H; Zhong, C; Peng, BZ; Zhang, ML; Li, BH; Huo, S; Guo, YJ; Ding, JP |
刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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出版日期 | 2007 |
卷号 | 282期号:20页码:15073-15080 |
通讯作者 | Ding, JP (reprint author), 800 Xiang Yin Rd, Shanghai 200433, Peoples R China.,jpding@sibs.ac.cn |
英文摘要 | Rituximab is a widely used monoclonal antibody drug for treating certain lymphomas and autoimmune diseases. To understand the molecular mechanism of recognition of human CD20 by Rituximab, we determined the crystal structure of the Rituximab Fab in complex with a synthesized peptide comprising the CD20 epitope ( residues 163-187) at 2.6-angstrom resolution. The combining site of the Fab consists of four complementarity determining regions that form a large, deep pocket to accommodate the epitope peptide. The bound peptide assumes a unique cyclic conformation that is constrained by a disulfide bond and a rigid proline residue ( Pro(172)). The (170)ANPS(173) motif of CD20 is deeply embedded into the pocket on the antibody surface and plays an essential role in the recognition and binding of Rituximab. The antigen-antibody interactions involve both hydrogen bonds and van der Waals contacts and display a high degree of structural and chemical complementarity. These results provide a molecular basis for the specific recognition of CD20 by Rituximab as well as valuable information for development of improved antibody drugs with better specificity and higher affinity. |
学科主题 | Biochemistry & Molecular Biology |
类目[WOS] | Biochemistry & Molecular Biology |
关键词[WOS] | MONOCLONAL-ANTIBODIES ; FINE SPECIFICITY ; MEMBRANE RAFTS ; LYMPHOMA ; ANTIGEN ; REDISTRIBUTION ; EPITOPES ; SEQUENCE ; CELLS |
收录类别 | SCI |
语种 | 英语 |
WOS记录号 | WOS:000246589000047 |
版本 | 出版稿 |
源URL | [http://202.127.25.143/handle/331003/1629] ![]() |
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. Structural basis for recognition of CD20 by therapeutic antibody rituximab[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2007,282(20):15073-15080. |
APA | Du, JM.,Wang, H.,Zhong, C.,Peng, BZ.,Zhang, ML.,...&Ding, JP.(2007).Structural basis for recognition of CD20 by therapeutic antibody rituximab.JOURNAL OF BIOLOGICAL CHEMISTRY,282(20),15073-15080. |
MLA | Du, JM,et al."Structural basis for recognition of CD20 by therapeutic antibody rituximab".JOURNAL OF BIOLOGICAL CHEMISTRY 282.20(2007):15073-15080. |
入库方式: OAI收割
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