Xingyue Guan, Yunqiang Bian, Zilong Guo, Jian Zhang, Yi Cao, Wenfei Li, Wei Wang
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Bidirectional Allostery Mechanism in Catch-Bond Formation of CD44 Mediated Cell Adhesion
Catch-bonds, whereby noncovalent ligand–receptor interactions are counterintuitively reinforced by tensile forces, play a major role in cell adhesion under mechanical stress. A basic prerequisite for catch-bond formation, as implicated in classic catch-bond models, is that force-induced remodeling of the ligand binding interface occurs prior to bond rupture. However, what strategy receptor proteins utilize to meet such specific kinetic control remains elusive. Here we report a bidirectional allostery mechanism of catch-bond formation based on theoretical and molecular dynamics simulation studies. Binding of ligand allosterically reduces the threshold force for unlocking of otherwise stably folded force-sensing element (i.e., forward allostery), so that a much smaller tensile force can trigger the conformational switching of receptor protein to high binding-strength state via backward allosteric coupling before bond rupture. Such bidirectional allostery fulfills the specific kinetic control required by catch-bond formation and is likely to be commonly utilized in cell adhesion. The essential thermodynamic and kinetic features of receptor proteins essential for catch-bond formation were identified.
期刊介绍:
The Journal of Physical Chemistry (JPC) Letters is devoted to reporting new and original experimental and theoretical basic research of interest to physical chemists, biophysical chemists, chemical physicists, physicists, material scientists, and engineers. An important criterion for acceptance is that the paper reports a significant scientific advance and/or physical insight such that rapid publication is essential. Two issues of JPC Letters are published each month.