IMECH-IR  > 国家微重力实验室
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)
Source PublicationFEBS JOURNAL
2018
Volume285Issue:2Pages:261-274
ISSN1742-464X
AbstractThe 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.
Keywordbeta(2) integrin allostery conformational stability force salt bridge interaction
DOI10.1111/febs.14335
URL查看原文
Indexed BySCI
Language英语
WOS IDWOS:000423416700005
WOS KeywordI-DOMAIN ; A-DOMAIN ; LEUKOCYTE INTEGRIN ; CRYSTAL-STRUCTURE ; OUTSIDE-IN ; ACTIVATION ; LIGAND ; CONFORMATION ; ADHESION ; AFFINITY
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
Funding OrganizationNational 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
Ranking1
Citation statistics
Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/77890
Collection国家微重力实验室
Affiliation1.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.
Files in This Item: Download All
File Name/Size DocType Version Access License
IrJ2018278.pdf(2053KB)期刊论文出版稿开放获取CC BY-NC-SAView Download
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[张潇]'s Articles
[Li LD]'s Articles
[李宁]'s Articles
Baidu academic
Similar articles in Baidu academic
[张潇]'s Articles
[Li LD]'s Articles
[李宁]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[张潇]'s Articles
[Li LD]'s Articles
[李宁]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: IrJ2018278.pdf
Format: Adobe PDF
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.