Structural Basis for the Blockage of IL-2 Signaling by Therapeutic Antibody Basiliximab
文献类型：期刊论文
| 作者 | Du, JM; Yang, H; Zhang, DP; Wang, JC; Guo, HZ; Peng, BZ; Guo, YJ; Ding, JP |
| 刊名 | JOURNAL OF IMMUNOLOGY
 |
| 出版日期 | 2010 |
| 卷号 | 184期号:3页码:1361-1368 |
| 通讯作者 | Ding, JP (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol, 320 Yue Yang Rd, Shanghai 200031, Peoples R China.,jpding@sibs.ac.cn |
| 英文摘要 | IL-2 signaling plays a central role in the initiation and activation of immune responses. Correspondingly, blockage of this pathway leads to inhibition of the immune system and would provide some therapeutic benefits. Basiliximab (Simulect), a therapeutic mAb drug with specificity against IL-2R alpha of T cells, was approved by U.S. Food and Drug Administration in 1998. It has been proven to be effective in the suppression of the IL-2 pathway and hence has been widely used to prevent allograft rejection in organ transplantation, especially in kidney transplants. In this study, we report the crystal structure of the basiliximab Fab in complex with the ectodomain of IL-2R alpha at 2.9 angstrom resolution. In the complex structure, the Fab interacts with IL-2R alpha with extensive hydrophobic and hydrophilic interactions, accounting for a high binding affinity of 0.14 nM. The Ag binding site of basiliximab consists of all six CDR loops that form a large binding interface with a central shallow hydrophobic groove surrounded by four hydrophilic patches. The discontinuous epitope is composed of several segments from the D1 domain and a minor segment from the D2 domain that overlap with most of the regions responsible for the interactions with IL-2. Thus, basiliximab binding can completely block the interactions of IL-2 with IL-2R alpha and hence inhibit the activation of the IL-2 signal pathway. The structural results also provide important implications for the development of improved and new IL-2R alpha-targeted mAb drugs. The Journal of Immunology, 2010, 184: 1361-1368. |
| 学科主题 | Immunology |
| 类目[WOS] | Immunology |
| 关键词[WOS] | INTERLEUKIN-2-RECEPTOR BETA-CHAIN ; CELL GROWTH-FACTOR ; GAMMA-CHAIN ; ALPHA-RECEPTOR ; ANTIGEN INTERACTIONS ; CYTOPLASMIC DOMAINS ; COMPLEX ; BINDING ; SPECIFICITY ; AFFINITY |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000273956400028 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/984]  |
| 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,Yang, H,Zhang, DP,et al. Structural Basis for the Blockage of IL-2 Signaling by Therapeutic Antibody Basiliximab[J]. JOURNAL OF IMMUNOLOGY,2010,184(3):1361-1368. |
| APA | Du, JM.,Yang, H.,Zhang, DP.,Wang, JC.,Guo, HZ.,...&Ding, JP.(2010).Structural Basis for the Blockage of IL-2 Signaling by Therapeutic Antibody Basiliximab.JOURNAL OF IMMUNOLOGY,184(3),1361-1368. |
| MLA | Du, JM,et al."Structural Basis for the Blockage of IL-2 Signaling by Therapeutic Antibody Basiliximab".JOURNAL OF IMMUNOLOGY 184.3(2010):1361-1368. |
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