Conformational Stability Analyses of Alpha Subunit I Domain of LFA-1 and Mac-1

	Conformational Stability Analyses of Alpha Subunit I Domain of LFA-1 and Mac-1
	Mao DB(毛德斌); Lv SQ(吕守芹); Li N(李宁); Zhang Y(章燕); Long M(龙勉)
刊名	PLOS One
	2011
通讯作者邮箱	lsq@imech.ac.cn; mlong@imech.ac.cn
卷号	6 期号:8 页码:e24188
关键词	A-Domain Molecular-Dynamics Structural Basis Integrin Activation Crystal-Structure Cell-Adhesion T-Cell Neutrophils Affinity Migration
ISSN号	1932-6203
通讯作者	Mao, DB (reprint author), Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Beijing 100080, Peoples R China
产权排序	[Mao, Debin; Lu, Shouqin; Li, Ning; Zhang, Yan; Long, Mian] Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Beijing 100080, Peoples R China; [Mao, Debin; Lu, Shouqin; Li, Ning; Zhang, Yan; Long, Mian] Chinese Acad Sci, Inst Mech, Natl Micrograv Lab, Beijing 100080, Peoples R China; [Mao, Debin; Lu, Shouqin; Li, Ning; Zhang, Yan; Long, Mian] Chinese Acad Sci, Inst Mech, Ctr Biomech & Bioengn, Beijing 100080, Peoples R China
中文摘要	beta(2) integrin of lymphocyte function-associated antigen-1 (LFA-1) or macrophage-1 antigen (Mac-1) binds to their common ligand of intercellular adhesion molecule-1 (ICAM-1) and mediates leukocyte-endothelial cell (EC) adhesions in inflammation cascade. Although the two integrins are known to have distinct functions, the corresponding micro-structural bases remain unclear. Here (steered-)molecular dynamics simulations were employed to elucidate the conformational stability of a subunit I domains of LFA-1 and Mac-1 in different affinity states and relevant I domain-ICAM-1 interaction features. Compared with low affinity (LA) Mac-1, the LA LFA-1 I domain was unstable in the presence or absence of ICAM-1 ligand, stemming from diverse orientations of its alpha(7)-helix with different motifs of zipper-like hydrophobic junction between alpha(1)- and alpha(7)-helices. Meanwhile, spontaneous transition of LFA-1 I domain from LA state to intermediate affinity (IA) state was first visualized. All the LA, IA, and high affinity (HA) states of LFA-1 I domain and HA Mac-1 I domain were able to bind to ICAM-1 ligand effectively, while LA Mac-1 I domain was unfavorable for binding ligand presumably due to the specific orientation of S144 side-chain that capped the MIDAS ion. These results furthered our understanding in correlating the structural bases with their functions of LFA-1 and Mac-1 integrins from the viewpoint of I domain conformational stability and of the characteristics of I domain-ICAM-1 interactions.
学科主题	Life Sciences & Biomedicine - Other Topics
分类号	二类/Q1
类目[WOS]	Multidisciplinary Sciences
研究领域[WOS]	Science & Technology - Other Topics
关键词[WOS]	A-DOMAIN ; MOLECULAR-DYNAMICS ; STRUCTURAL BASIS ; INTEGRIN ACTIVATION ; CRYSTAL-STRUCTURE ; CELL-ADHESION ; T-CELL ; NEUTROPHILS ; AFFINITY ; MIGRATION
收录类别	SCI
资助信息	This work was supported by National Natural Science Foundation of China grants 30730032 and 11072251 (www.nsfc.gov.cn), National Key Basic Research Foundation of China grant 2011CB710904 (www.most.gov.cn), and CAS Knowledge Innovation Program grant KJCX2-YW-L08 and Scientific Research Equipment Project of grant Y2010030 (http://english.cas.cn). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
原文出处	http://dx.doi.org/10.1371/journal.pone.0024188
语种	英语
WOS记录号	WOS:000294680800064
公开日期	2012-04-01
内容类型	期刊论文
源URL	[http://dspace.imech.ac.cn/handle/311007/45079]
专题	力学研究所_国家微重力实验室
推荐引用方式 GB/T 7714	Mao DB,Lv SQ,Li N,et al. Conformational Stability Analyses of Alpha Subunit I Domain of LFA-1 and Mac-1[J]. PLOS One,2011,6(8):e24188.
APA	毛德斌,吕守芹,李宁,章燕,&龙勉.(2011).Conformational Stability Analyses of Alpha Subunit I Domain of LFA-1 and Mac-1.PLOS One,6(8),e24188.
MLA	毛德斌,et al."Conformational Stability Analyses of Alpha Subunit I Domain of LFA-1 and Mac-1".PLOS One 6.8(2011):e24188.