The hydrophobic contacts between the center of the beta I domain and the alpha 1/alpha 7 helices are crucial for the low-affinity state of integrin alpha(4)beta(7)
文献类型：期刊论文
| 作者 | Liu, Jie1; Fu, Ting2; Peng, Bo1; Sun, Hao1; Chu, HuiYing2; Li, GuoHui2; Chen, JianFeng1 |
| 刊名 | febs journal
 |
| 出版日期 | 2014-07-01 |
| 卷号 | 281期号:13页码:2915-2926 |
| 关键词 | affinity cell adhesion hydrophobic contacts integrin molecular dynamic simulation |
| 通讯作者 | 李国辉 |
| 英文摘要 | 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). integrin activation is associated with allosteric reshaping in the beta subunit i (beta i) domain. a prominently conformational change comprises displacement of the alpha 1 and alpha 7 helices in the beta i domain, suggesting that the location of these helices is important for the change in integrin affinity. in the present study, we report that the hydrophobic contacts between the center of the beta i-7 domain and the alpha 1/alpha 7 helices play critical roles in keeping alpha(4)beta(7) in a low-affinity state. using molecular dynamics simulation, we identified nine hydrophobic residues that might be involved in the critical hydrophobic contacts maintaining integrin in a low-affinity state. integrin beta 7i domain exhibited a lower binding free energy for ligand after disrupting these hydrophobic contacts by substituting the hydrophobic residues with ala. moreover, these alpha(4)beta(7) mutants not only showed high-affinity binding to soluble madcam-1, but also demonstrated firm cell adhesion to immobilized madcam-1 in shear flow and enhanced the strength of the alpha(4)beta(7)-madcam-1 interaction. disruption of the hydrophobic contacts also induced the active conformation of alpha(4)beta(7). thus, the findings obtained in the present study reveal an important structural basis for the low-affinity state of integrin. |
| WOS标题词 | science & technology ; life sciences & biomedicine |
| 学科主题 | 物理化学 |
| 类目[WOS] | biochemistry & molecular biology |
| 研究领域[WOS] | biochemistry & molecular biology |
| 关键词[WOS] | ion binding-sites ; molecular-dynamics ; monoclonal-antibody ; ligand recognition ; hybrid domain ; firm adhesion ; a-domain ; activation ; adhesiveness ; mutagenesis |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000339097600003 |
| 公开日期 | 2016-05-09 |
| 源URL | [http://cas-ir.dicp.ac.cn/handle/321008/144096]  |
| 专题 | 大连化学物理研究所_中国科学院大连化学物理研究所 |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Beijing 100864, Peoples R China 2.Chinese Acad Sci, Dalian Inst Chem Phys, Lab Mol Modeling & Design, State Key Lab Mol React Dynam, Beijing 100864, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Jie,Fu, Ting,Peng, Bo,et al. The hydrophobic contacts between the center of the beta I domain and the alpha 1/alpha 7 helices are crucial for the low-affinity state of integrin alpha(4)beta(7)[J]. febs journal,2014,281(13):2915-2926. |
| APA | Liu, Jie.,Fu, Ting.,Peng, Bo.,Sun, Hao.,Chu, HuiYing.,...&Chen, JianFeng.(2014).The hydrophobic contacts between the center of the beta I domain and the alpha 1/alpha 7 helices are crucial for the low-affinity state of integrin alpha(4)beta(7).febs journal,281(13),2915-2926. |
| MLA | Liu, Jie,et al."The hydrophobic contacts between the center of the beta I domain and the alpha 1/alpha 7 helices are crucial for the low-affinity state of integrin alpha(4)beta(7)".febs journal 281.13(2014):2915-2926. |
入库方式： OAI收割
来源：大连化学物理研究所
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