Molecular basis of the dynamic strength of the sialyl Lewis X--selectin interaction.
The selectins are Ca(2+)-dependent cell adhesion molecules that facilitate the initial attachment of leukocytes to the vascular endothelium by binding to a carbohydrate moiety as exemplified by the tetrasaccharide, sialyl Lewis X (sLeX). An important property of the selectin-sLeX interaction is its ability to withstand the hydrodynamic force of the blood flow. Herein, we used single-molecule dynamic force spectroscopy (DFS) to identify the molecular determinants within sLeX that give rise to the dynamic properties of the selectin/sLeX interaction. Our atomic force microscopy (AFM) measurements revealed that the unbinding of the selectin/sLeX complexes involves overcoming at least two activation barriers. The inner barrier, which determines the dynamic response of the complex at high forces, is governed by the interaction between the Fuc residue of sLeX and a Ca2+ ion chelated to the lectin domain of the selectin molecule, whereas the outer activation barrier can be attributed to interactions involving the sialic acid residue of sLeX. Due to their steep inner activation barriers, the selectin-sLeX complexes are less sensitive to high pulling forces. Hence, besides its contribution to the bond energy, the Ca2+ ion also grants the selectin-sLeX complexes a tensile strength that is crucial for the selectin-mediated rolling of leukocytes.
Zhang
Xiaohui
X
Department of Physiology and Biophysics, University of Miami School of Medicine, Miami, USA.
Bogorin
Daniela F
DF
Moy
Vincent T
VT
D002118:Calcium / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000502:physiology*; D004492:Edetic Acid / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D007983:Lewis Blood Group Antigens; D008024:Ligands; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D009844:Oligosaccharides / Q000737:chemistry / Q000378:metabolism*; D010504:Periodic Acid / Q000737:chemistry / Q000494:pharmacology; D019087:Selectins / Q000737:chemistry / Q000378:metabolism*; D000080506:Sialyl Lewis X Antigen
D007983:Lewis Blood Group Antigens; D008024:Ligands; D009844:Oligosaccharides; D019087:Selectins; D000080506:Sialyl Lewis X Antigen; D010504:Periodic Acid; D004492:Edetic Acid; D002118:Calcium