Tyrosine replacement of PSGL-1 reduces association kinetics with P- and L-selectin on the cell membrane

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	Tyrosine replacement of PSGL-1 reduces association kinetics with P- and L-selectin on the cell membrane
	Xiao BT(肖波涛); Tong CF(佟春芳); Jia XL(贾潇凌); Guo R(郭瑞); Lv SQ(吕守芹); Zhang Y(章燕); McEver RP; Zhu C; Long M(龙勉); Long, MA; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Beijing 100080, Peoples R China.
发表期刊	BIOPHYSICAL JOURNAL
	2012-08-22
卷号	103 期号:4 页码:777-785
ISSN	0006-3495
摘要	Binding of selectins to P-selectin glycoprotein ligand-1 (PSGL-1) mediates tethering and rolling of leukocytes on the endothelium during inflammation. Previous measurements obtained with a flow-chamber assay have shown that mutations of three tyrosines at the PSGL-1 N-terminus (Y46, Y48, and Y51) increase the reverse rates and their sensitivity to the force of bonds with P- and L-selectin. However, the effects of these mutations on the binding affinities and forward rates have not been studied. We quantified these effects by using an adhesion frequency assay to measure two-dimensional affinity and kinetic rates at zero force. Wild-type PSGL-1 has 2.2- to 8.5-fold higher binding affinities for P- and L-selectin than PSGL-1 mutants with two of three tyrosines substituted by phenylalanines, and 9.6- to 49-fold higher affinities than the PSGL-1 mutant with all three tyrosines replaced. In descending order, the affinity decreased from wild-type to Y48/51F, Y46/51F, Y46/48F, and Y46/48/51F. The affinity difference's were attributed to major changes in the forward rate and minor changes in the reverse rate, suggesting that these tyrosines regulate the accessibility of PSGL-1 to P- and L-selectin via electrostatic interactions, which is supported by molecular-dynamics simulations. Our results provide insights into the structure-function relationship of receptor-ligand binding at a single-residue level.
关键词	Ligand Binding-kinetics Glycoprotein Ligand-1 Molecular-dynamics Adhesion Sulfation Proteins Glycosulfopeptides Identification Dissociation Recognition
学科领域	生物力学
URL	查看原文
收录类别	SCI
语种	英语
WOS记录号	WOS:000307799100017
项目资助者	This work was supported by the National Natural Science Foundation of China (grants 30730032, 11072251, and 10902117), the National Key Basic Research Foundation of China (grants 2011CB710904 and 2006CB910303), the Strategic Priority Research Program (grants XDA01030102 and XDA04020219), the Knowledge Innovation Program of the Chinese Academy of Sciences (grant 2005-1-16 to M.L.), and the National Institutes of Health (grants AI77343 to C.Z. and R.P.M., HL090923 to R.P.M., and TW 05774-01 to C.Z. and M.L.).
课题组名称	NML分子-细胞生物力学与空间生命科学
论文分区	一类
引用统计	被引频次：11[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://dspace.imech.ac.cn/handle/311007/46605
专题	微重力重点实验室
通讯作者	Long, MA; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Beijing 100080, Peoples R China.
推荐引用方式 GB/T 7714	Xiao BT,Tong CF,Jia XL,et al. Tyrosine replacement of PSGL-1 reduces association kinetics with P- and L-selectin on the cell membrane[J]. BIOPHYSICAL JOURNAL,2012,103,4,:777-785.
APA	Xiao BT.,Tong CF.,Jia XL.,Guo R.,Lv SQ.,...&Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Beijing 100080, Peoples R China..(2012).Tyrosine replacement of PSGL-1 reduces association kinetics with P- and L-selectin on the cell membrane.BIOPHYSICAL JOURNAL,103(4),777-785.
MLA	Xiao BT,et al."Tyrosine replacement of PSGL-1 reduces association kinetics with P- and L-selectin on the cell membrane".BIOPHYSICAL JOURNAL 103.4(2012):777-785.

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