| Salt bridge interactions within the beta(2) integrin alpha(7) helix mediate force-induced binding and shear resistance ability | |
Zhang X(张潇) ; Li LD; Li N(李宁); Shu XY; Zhou LW(周吕文); Lv SQ(吕守芹); Chen SB; Mao DB; Long M(龙勉)
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| Source Publication | FEBS JOURNAL
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| 2018 | |
| Volume | 285Issue:2Pages:261-274 |
| ISSN | 1742-464X |
| Abstract | The functional performance of the alpha I domain alpha(7) helix in beta(2) integrin activation depends on the allostery of the alpha(7) helix, which axially slides down; therefore, it is critical to elucidate what factors regulate the allostery. In this study, we determined that there were two conservative salt bridge interaction pairs that constrain both the upper and bottom ends of the alpha(7) helix. Molecular dynamics (MD) simulations for three beta(2) integrin members, lymphocyte function-associated antigen-1 (LFA-1; alpha(L)beta(2)), macrophage-1 antigen (Mac-1; alpha(M)beta(2)) and alpha(x)beta(2), indicated that the magnitude of the salt bridge interaction is related to the stability of the alpha I domain and the strength of the corresponding force-induced allostery. The disruption of the salt bridge interaction, especially with double mutations in both salt bridges, significantly reduced the force-induced allostery time for all three members. The effects of salt bridge interactions of the alpha I domain alpha(7) helix on beta(2) integrin conformational stability and allostery were experimentally validated using Mac-1 constructs. The results demonstrated that salt bridge mutations did not alter the conformational state of Mac-1, but they did increase the force-induced ligand binding and shear resistance ability, which was consistent with MD simulations. This study offers new insight into the importance of salt bridge interaction constraints of the alpha I domain alpha(7) helix and external force for beta(2) integrin function. |
| Keyword | beta(2) integrin allostery conformational stability force salt bridge interaction |
| DOI | 10.1111/febs.14335 |
| URL | 查看原文 |
| Indexed By | SCI |
| Language | 英语 |
| WOS ID | WOS:000423416700005 |
| WOS Keyword | I-DOMAIN ; A-DOMAIN ; LEUKOCYTE INTEGRIN ; CRYSTAL-STRUCTURE ; OUTSIDE-IN ; ACTIVATION ; LIGAND ; CONFORMATION ; ADHESION ; AFFINITY |
| WOS Research Area | Biochemistry & Molecular Biology |
| WOS Subject | Biochemistry & Molecular Biology |
| Funding Organization | National Natural Science Foundation of China [31230027, 91642203, 11372332] ; National Key Research and Development Program of China [2016YFA0501601] ; Strategic Priority Research Program of Chinese Academy of Sciences [XDB22040101] |
| Classification | 二类/Q1 |
| Ranking | 1 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://dspace.imech.ac.cn/handle/311007/77890 |
| Collection | 微重力重点实验室 |
| Affiliation | 1.Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing, Peoples R China 2.Chinese Acad Sci, Inst Mech, Natl Micrograv Lab, Key Lab Micrograv, Beijing, Peoples R China 3.Chinese Acad Sci, Inst Mech, Beijing Key Lab Engn Construct & Mechanobiol, Beijing, Peoples R China 4.Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China 5.Chongqing Univ, Coll Bioengn, Chongqing, Peoples R China |
| Recommended Citation GB/T 7714 | Zhang X,Li LD,Li N,et al. Salt bridge interactions within the beta(2) integrin alpha(7) helix mediate force-induced binding and shear resistance ability[J]. FEBS JOURNAL,2018,285,2,:261-274. |
| APA | 张潇.,Li LD.,李宁.,Shu XY.,周吕文.,...&龙勉.(2018).Salt bridge interactions within the beta(2) integrin alpha(7) helix mediate force-induced binding and shear resistance ability.FEBS JOURNAL,285(2),261-274. |
| MLA | 张潇,et al."Salt bridge interactions within the beta(2) integrin alpha(7) helix mediate force-induced binding and shear resistance ability".FEBS JOURNAL 285.2(2018):261-274. |
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| IrJ2018278.pdf（2053KB） | 期刊论文 | 出版稿 | 开放获取 | CC BY-NC-SA | View Download | |
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