Dynamics of unbinding of cell adhesion molecules: transition from catch to slip bonds.
The unbinding dynamics of complexes involving cell-adhesion molecules depends on the specific ligands. Atomic force microscopy measurements have shown that for the specific P-selectin-P-selectin glycoprotein ligand (sPSGL-1) the average bond lifetime t initially increases (catch bonds) at low (< or =10 pN) constant force, f, and decreases when f > 10 pN (slip bonds). In contrast, for the complex with G1 anti-P-selectin monoclonal antibody t monotonically decreases with f. To quantitatively map the energy landscape of such complexes we use a model that considers the possibility of redistribution of population from one force-free state to another force-stabilized bound state. The excellent agreement between theory and experiments allows us to extract energy landscape parameters by fitting the calculated curves to the lifetime measurements for both sPSGL-1 and G1. Surprisingly, the unbinding transition state for P-selectin-G1 complex is close (0.32 nm) to the bound state, implying that the interaction is brittle, i.e., once deformed, the complex fractures. In contrast, the unbinding transition state of the P-selectin-sPSGL-1 complex is far (approximately 1.5 nm) from the bound state, indicative of a compliant structure. Constant f energy landscape parameters are used to compute the distributions of unbinding times and unbinding forces as a function of the loading rate, rf. For a given rf, unbinding of sPSGL-1 occurs over a broader range of f with the most probable f being an order of magnitude less than for G1. The theory for cell adhesion complexes can be used to predict the outcomes of unbinding of other protein-protein complexes.
Barsegov
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Institute for Physical Science and Technology, University of Maryland, College Park, MD 20742, USA.
Thirumalai
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D008024:Ligands; D046911:Macromolecular Substances; D008433:Mathematics; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008962:Models, Theoretical; D019007:P-Selectin / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
D008024:Ligands; D046911:Macromolecular Substances; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein