An anti-urokinase plasminogen activator receptor (uPAR) antibody: Crystal structure and binding epitope
文献类型：期刊论文
| 作者 | Y. D. Li ; G. Parry ; L. Q. Chen ; J. A. Callahan ; D. E. Shaw ; E. J. Meehan ; A. P. Mazar ; M. D. Huang |
| 刊名 | Journal of Molecular Biology
 |
| 出版日期 | 2007-01 |
| 卷号 | 365期号:4页码:1117-1129 |
| 关键词 | antibody crystal structure uPAR ATN615 Fab breast-cancer tumor-growth in-vivo prognostic-significance inhibitory antibody colorectal-cancer integrin function potential target lysozyme complex cells |
| ISSN号 | 0022-2836 |
| 中文摘要 | Human urokinase-type plasminogen activator receptor (uPAR/CD87) is expressed at the invasive interface of the tumor-stromal microenvironment in many human cancers and interacts with a wide array of extracellular molecules. An anti-uPAR antibody (ATN615) was prepared using hybridoma technology. This antibody binds to uPAR in vitro with high affinity (K-d similar to 1 nM) and does not interfere with uPA binding to uPAR. Pere we crystal structure of the Fab fragment of ATN615 at 1.77 angstrom and the report the crystal analysis of ATN615-suPAR-ATF structure that was previously determined, emphasizing the ATN615-suPAR interaction. The complementarity determining (CDRs) of ATN615 consist of a high percentage of aromatic residues, and form a relatively flat and undulating surface. The ATN615 Fab fragment recognizes domain 3 of suPAR. The antibody-antigen recognition involves 11 suPAR residues and 12 Fab residues from five CDRs. Structural data suggest that Pro188, Asn190, Gly191, and Arg192 residues of uPAR are the key residues for the antibody recognition, while Pro189 and Arg192 render specificity of ATN615 for human uPAR. Interestingly, this antibody-antigen interface has a small contact area, mainly polar interaction with little hydrophobic character, yet has high binding strength. Furthermore, several solvent molecules (assigned as polyethylene glycols) were clearly visible in the binding interface between antibody and antigen, suggesting that solvent molecules may be important for the maximal binding between suPAR and ATN615 Fab. ATN615 undergoes small but noticeable changes in its CDR region upon antigen binding. (c) 2006 Elsevier Ltd. All rights reserved. |
| 语种 | 英语 |
| 公开日期 | 2013-04-01 |
| 源URL | [http://ir.fjirsm.ac.cn/handle/350002/6435]  |
| 专题 | 福建物质结构研究所_中科院福建物质结构研究所_期刊论文 |
| 推荐引用方式 GB/T 7714 | Y. D. Li,G. Parry,L. Q. Chen,et al. An anti-urokinase plasminogen activator receptor (uPAR) antibody: Crystal structure and binding epitope[J]. Journal of Molecular Biology,2007,365(4):1117-1129. |
| APA | Y. D. Li.,G. Parry.,L. Q. Chen.,J. A. Callahan.,D. E. Shaw.,...&M. D. Huang.(2007).An anti-urokinase plasminogen activator receptor (uPAR) antibody: Crystal structure and binding epitope.Journal of Molecular Biology,365(4),1117-1129. |
| MLA | Y. D. Li,et al."An anti-urokinase plasminogen activator receptor (uPAR) antibody: Crystal structure and binding epitope".Journal of Molecular Biology 365.4(2007):1117-1129. |
入库方式： OAI收割
来源：福建物质结构研究所
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。