{Reference Type}: Journal Article
{Title}: Topology of molecular deformations induces triphasic catch bonding in selectin-ligand bonds.
{Author}: Barkan CO;Bruinsma RF;
{Journal}: Proc Natl Acad Sci U S A
{Volume}: 121
{Issue}: 6
{Year}: 2024 Feb 6
{Factor}: 12.779
{DOI}: 10.1073/pnas.2315866121
{Abstract}: Among the long-standing efforts to elucidate the physical mechanisms of protein-ligand catch bonding, particular attention has been directed at the family of selectin proteins. Selectins exhibit slip, catch-slip, and slip-catch-slip bonding, with minor structural modifications causing major changes in selectins' response to force. How can a single structural mechanism allow interconversion between these various behaviors? We present a unifying theory of selectin-ligand catch bonding, using a structurally motivated free energy landscape to show how the topology of force-induced deformations of the molecular system produces the full range of observed behaviors. We find that the pathway of bond rupture deforms in non-trivial ways, such that unbinding dynamics depend sensitively on force. This implies a severe breakdown of Bell's theory-a paradigmatic theory used widely in catch bond modeling-raising questions about the suitability of Bell's theory in modeling other catch bonds. Our approach can be applied broadly to other protein-ligand systems.