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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.
Source PublicationBIOPHYSICAL JOURNAL
2012-08-22
Volume103Issue:4Pages:777-785
ISSN0006-3495
AbstractBinding 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.
KeywordLigand Binding-kinetics Glycoprotein Ligand-1 Molecular-dynamics Adhesion Sulfation Proteins Glycosulfopeptides Identification Dissociation Recognition
Subject Area生物力学
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Indexed BySCI
Language英语
WOS IDWOS:000307799100017
Funding OrganizationThis 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.).
DepartmentNML分子-细胞生物力学与空间生命科学
Classification一类
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Cited Times:8[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://dspace.imech.ac.cn/handle/311007/46605
Collection国家微重力实验室
Corresponding AuthorLong, MA; Chinese Acad Sci, Inst Mech, Key Lab Micrograv, Beijing 100080, Peoples R China.
Recommended Citation
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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