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Topology of molecular deformations induces triphasic catch bonding in selectin-ligand bonds.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 2/6/2024, Vol. 121 Issue 6, p1-8, 17p
- Publication Year :
- 2024
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- SELECTINS
TOPOLOGY
SWITCHING theory
MODEL theory
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 121
- Issue :
- 6
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 175487388
- Full Text :
- https://doi.org/10.1073/pnas.2315866121