| 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.
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| Source Publication | BIOPHYSICAL JOURNAL
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| 2012-08-22 | |
| Volume | 103Issue:4Pages:777-785 |
| ISSN | 0006-3495 |
| Abstract | 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. |
| Keyword | Ligand Binding-kinetics Glycoprotein Ligand-1 Molecular-dynamics Adhesion Sulfation Proteins Glycosulfopeptides Identification Dissociation Recognition |
| Subject Area | 生物力学 |
| URL | 查看原文 |
| Indexed By | SCI |
| Language | 英语 |
| WOS ID | WOS:000307799100017 |
| Funding Organization | 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.). |
| Department | NML分子-细胞生物力学与空间生命科学 |
| Classification | 一类 |
| Citation statistics | |
| Document Type | 期刊论文 |
| Identifier | http://dspace.imech.ac.cn/handle/311007/46605 |
| Collection | 微重力重点实验室 |
| Corresponding Author | Long, 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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