Mechanically Regulated Outside-In Activation of an I-Domain-Containing Integrin
文献类型：期刊论文
| 作者 | Mao DB(毛德斌)1,2,3 ; Lv SQ(吕守芹)1,2,3; Zhang X(张潇)1,2,3; Long M(龙勉)1,2,3
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| 刊名 | BIOPHYSICAL JOURNAL
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| 出版日期 | 2020-09-01 |
| 卷号 | 119期号:5页码:966-977 |
| ISSN号 | 0006-3495 |
| DOI | 10.1016/j.bpj.2020.07.022 |
| 通讯作者 | Lu, Shouqin(lsq@imech.ac.cn) ; Long, Mian(mlong@imech.ac.cn) |
| 英文摘要 | Integrins are heterodimeric transmembrane proteins that mediate cellular adhesion and bidirectional mechanotransductions through their conformational allostery. The allosteric pathway of an I-domain-containing integrin remains unclear because of its complexity and lack of effective experiments. For a typical I-domain-containing integrin alpha(x)beta(2), molecular dynamics simulations were employed here to investigate the conformational dynamics in the first two steps of outside-in activation, the bindings of both the external and internal ligands. Results showed that the internal ligand binding is a prerequisite to the allosteric transmission from the alpha- to beta-subunits and the exertion of external force to integrin-ligand complex. The opening state of alpha l domain with downward movement and lower half unfolding of alpha(7)-helix ensures the stable intersubunit conformational transmission through external ligand binding first and internal ligand binding later. Reverse binding order induces a, to our knowledge, novel but unstable swingout of beta-subunit Hybrid domain with the retained close states of both alpha l and beta l domains. Prebinding of external ligand greatly facilitates the following internal ligand binding and vice versa. These simulations furthered the under-standing in the outside-in activation of I-domain-containing integrins from the viewpoint of internal allosteric pathways. |
| 分类号 | 一类/力学重要期刊 |
| WOS关键词 | STRUCTURAL BASIS ; LEUKOCYTE INTEGRIN ; INTERNAL LIGAND ; A-DOMAIN ; AFFINITY ; BINDING ; DYNAMICS ; STATE ; CONFORMATION ; RECOGNITION |
| 资助项目 | National Key Research and Development Program of China[2016YFA0501601] ; National Natural Science Foundation of China[91642203] ; National Natural Science Foundation of China[31627804] ; National Natural Science Foundation of China[11972042] ; Frontier Science Key Project of Chinese Academy of Sciences[QYZDJ-SSW-JSC018] ; Scientific Instrument Developing Project of Chinese Academy of Sciences[GJJSTU20190005] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDB22040101] |
| WOS研究方向 | Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:000565024300009 |
| 资助机构 | National Key Research and Development Program of China ; National Natural Science Foundation of China ; Frontier Science Key Project of Chinese Academy of Sciences ; Scientific Instrument Developing Project of Chinese Academy of Sciences ; Strategic Priority Research Program of Chinese Academy of Sciences |
| 其他责任者 | Lu, Shouqin ; Long, Mian |
| 源URL | [http://dspace.imech.ac.cn/handle/311007/85022]  |
| 专题 | 力学研究所_国家微重力实验室 |
| 作者单位 | 1.Univ Chinese Acad Sci, Sch Engn Sci, Beijing, Peoples R China 2.Chinese Acad Sci, Inst Mech, CAS Ctr Excellence Complex Syst Mech, Beijing, Peoples R China; 3.Chinese Acad Sci, Ctr Biomech & Bioengn, Beijing Key Lab Engn Construct & Mechanobiol, Key Lab Micrograv,Natl Micrograv Lab, Beijing, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Mao DB,Lv SQ,Zhang X,et al. Mechanically Regulated Outside-In Activation of an I-Domain-Containing Integrin[J]. BIOPHYSICAL JOURNAL,2020,119(5):966-977. |
| APA | 毛德斌,吕守芹,张潇,&龙勉.(2020).Mechanically Regulated Outside-In Activation of an I-Domain-Containing Integrin.BIOPHYSICAL JOURNAL,119(5),966-977. |
| MLA | 毛德斌,et al."Mechanically Regulated Outside-In Activation of an I-Domain-Containing Integrin".BIOPHYSICAL JOURNAL 119.5(2020):966-977. |
入库方式： OAI收割
来源：力学研究所
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