The CC ' and DE Loops in Ig Domains 1 and 2 of MAdCAM-1 Play Different Roles in MAdCAM-1 Binding to Low- and High-affinity Integrin alpha(4)beta(7)
文献类型：期刊论文
| 作者 | Sun, H; Wu, YM; Qi, JP; Pan, YD; Ge, GX; Chen, JF |
| 刊名 | JOURNAL OF BIOLOGICAL CHEMISTRY
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| 出版日期 | 2011 |
| 卷号 | 286期号:14页码:42006 |
| 通讯作者 | Chen, JF (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, 320 YueYang Rd, Shanghai 200031, Peoples R China.,jfchen@sibs.ac.cn |
| 英文摘要 | Lymphocyte homing is regulated by the dynamic interaction between integrins and their ligands. Integrin alpha(4)beta(7) mediates both rolling and firm adhesion of lymphocytes by modulating its affinity to the ligand, mucosal addressin cell adhesion molecule-1 (MAdCAM-1). Although previous studies have revealed some mechanisms of alpha(4)beta(7)-MAdCAM-1 binding, little is known about the different molecular bases of the low- and high-affinity alpha(4)beta(7)-MAdCAM-1 interactions, which mediate rolling and firm adhesion of lymphocytes, respectively. Here, we found that two loops in immunoglobulin domains 1 and 2 (D1 and D2) of MAdCAM-1 played different roles in MAdCAM-1 binding to low-affinity (inactive) and high-affinity (activated) alpha(4)beta(7). The Asp-42 in the CC` loop of D1 was indispensable for MAdCAM-1 binding to both low-affinity and high-affinity alpha(4)beta(7). The other CC` loop residues except for Arg-39 and Ser-44 were essential for MAdCAM-1 binding to both inactive alpha(4)beta(7) and alpha(4)beta(7) activated by SDF-1 alpha or talin, but not required for MAdCAM-1 binding to Mn2+-activated alpha(4)beta(7). Single amino acid substitution of the DE loop residues mildly decreased MAdCAM-1 binding to both inactive and activated alpha(4)beta(7). Notably, removal of the DE loop greatly impaired MAdCAM-1 binding to inactive and SDF-1 alpha- or talin-activated alpha(4)beta(7), but only decreased 60% of MAdCAM-1 binding to Mn2+-activated alpha(4)beta(7). Moreover, DE loop residues were important for stabilizing the low-affinity alpha(4)beta(7)-MAdCAM-1 interaction. Thus, our findings demonstrate the distinct roles of the CC` and DE loops in the recognition of MAdCAM-1 by low-and high-affinity alpha(4)beta(7) and suggest that the inactive alpha(4)beta(7) and alpha(4)beta(7) activated by different stimuli have distinct conformations with different structural requirements for MAdCAM-1 binding. |
| 学科主题 | Biochemistry & Molecular Biology |
| 类目[WOS] | Biochemistry & Molecular Biology |
| 关键词[WOS] | CELL-ADHESION MOLECULE-1 ; CRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; FIRM ADHESION ; RECOGNITION ; IMMUNOGLOBULIN ; SUBUNIT ; SITES ; LYMPHOCYTES ; SPECIFICITY |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000289077500023 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.143/handle/331003/876]  |
| 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 | Sun, H,Wu, YM,Qi, JP,et al. The CC ' and DE Loops in Ig Domains 1 and 2 of MAdCAM-1 Play Different Roles in MAdCAM-1 Binding to Low- and High-affinity Integrin alpha(4)beta(7)[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2011,286(14):42006. |
| APA | Sun, H,Wu, YM,Qi, JP,Pan, YD,Ge, GX,&Chen, JF.(2011).The CC ' and DE Loops in Ig Domains 1 and 2 of MAdCAM-1 Play Different Roles in MAdCAM-1 Binding to Low- and High-affinity Integrin alpha(4)beta(7).JOURNAL OF BIOLOGICAL CHEMISTRY,286(14),42006. |
| MLA | Sun, H,et al."The CC ' and DE Loops in Ig Domains 1 and 2 of MAdCAM-1 Play Different Roles in MAdCAM-1 Binding to Low- and High-affinity Integrin alpha(4)beta(7)".JOURNAL OF BIOLOGICAL CHEMISTRY 286.14(2011):42006. |
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