Lectin domain peptides from selectins interact with both cell surface ligands and Ca2+ ions.
Selectins are receptors that mediate leukocyte adhesion to platelets or endothelial cells through Ca(2+)-dependent interactions with cell surface oligosaccharides. We found that peptides corresponding to residues 23-30, 54-63, and 70-79 of the N-terminal lectin domain of P-selectin inhibited leukocyte adhesion to P-selectin. Peptides corresponding to the homologous 23-30 and 54-63 regions of E-selectin and L-selectin also prevented cell binding to P-selectin. Immobilized albumin conjugates of the three P-selectin peptides supported adhesion of myeloid cells and certain other cells expressing fucosylated oligosaccharides. Ca2+ was required for optimal cell adhesion to the conjugates containing the 23-30 and 54-63 sequences. Furthermore, Ca2+ interacted with the 23-30 and 54-63 peptides of all three selectins, as detected by changes in intrinsic fluorescence emission intensity. These data suggest that residues contained within the 23-30 and 54-63 regions of the selectins represent contact sites for carbohydrate structures on target cells. Furthermore, binding of Ca2+ to these sequences may directly enhance their ability to interact with cell surface ligands.
Geng
J G
JG
Department of Medicine, W. K. Warren Medical Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City.
Heavner
G A
GA
McEver
R P
RP
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D037102:Lectins / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000378:metabolism; D019007:P-Selectin; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*
D002413:Cations, Divalent; D015815:Cell Adhesion Molecules; D037102:Lectins; D008024:Ligands; D009844:Oligosaccharides; D019007:P-Selectin; D010455:Peptides; D010980:Platelet Membrane Glycoproteins; D002118:Calcium