title: The two-pathway model of the biological catch-bond as a limit of the allosteric model.
abstract: Catch-binding is a counterintuitive phenomenon in which the lifetime of a receptor/ligand bond increases when a force is applied to break the bond. Several mechanisms have been proposed to rationalize catch-binding. In the two-pathway model, the force drives the system away from its native dissociation pathway into an alternative pathway involving a higher energy barrier. Here, we analyze an allosteric model suggesting that a force applied to the complex alters the distribution of receptor conformations, and as a result, induces changes in the ligand-binding site. The model assumes explicitly that the allosteric transitions govern the properties of the ligand site. We demonstrate that the dynamics of the ligand is described by two relaxation times, one of which arises from the allosteric site. Therefore, we argue that one can characterize the allosteric transitions by studying the receptor/ligand binding. We show that the allosteric description reduces to the two-pathway model in the limit when the allosteric transitions are faster than the bond dissociation. The formal results are illustrated with two systems, P-selectin/PSGL-1 and FimH/mannose, subjected to both constant and time-dependent forces. The report advances our understanding of catch-binding by combining alternative physical models into a unified description and makes the problem more tractable for the bond mechanics community.
authors: Department of Chemistry, University of Rochester, Rochester, New York, USA.
authors: Yuriy V
authors: YV
authors: Pereverzev
authors: Eugenia
authors: E
authors: Prezhdo
authors: Evgeni V
authors: EV
authors: Sokurenko
mesh_terms: D000494:Allosteric Regulation; D001696:Biomechanical Phenomena; D036781:Fimbriae Proteins / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008024:Ligands; D008358:Mannose / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism; D008954:Models, Biological; D019007:P-Selectin / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding
chemical_list: D008024:Ligands; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D036781:Fimbriae Proteins; D008358:Mannose