作者：Yang; Liu; Xianbin; Lei; Jiayun; Liu; ...vonphysicalmodelssinglewillebrandfactora1domaingpib
摘要：Von Willebrand Factor(VWF)is a concatameric glycoprotein that plays a key role in rapid hemostasis and thrombosis.VWF has different functional domains that can bind to various molecules such as collagen,hemostatic factorⅧ,integrin,and platelet glycoprotein lbα(GPlbα)to achieve multiple biological functions.During hemostasis,the A1 domain of VWF binds to GPIbαwhere platelets accumulate in the injured vascular endothelium.Due to forces generated by the hemodynamic gradient flow,the relations of bond-dissociation rates versus forces show that the lifetime of molecular bond has multiple states under the external force.We processed the experimental data of receptor-ligand in a single molecule obtained from optical tweezers by two different methods,including a Dudko-Hummer-Szabo equation,and another method combining force4ime history and force induced bond rupture.Then we used a recently developed physical equation regarding protein unfolding rate to fit our results.The lifetime of the bond between A1 and GPlbαobtained by the above mentioned two methods shows a'three-stage'change upon gradually increasing the external force.When the external force was below 8 pN,the lifetime of the bond deceased as the external force increased,which is a typical expression of a catch bond.The lifetime of the bond started to increase when the external force increased from 8 to 11 pN,and then decrease again when the external force increased to above 11 pN.Kim et al.used different processing methods and proposes a'flex-bond'model:the lifetime of the bond will decrease as the external force increases,then suddenly increase to a peak,and continue to decrease with the increase of force.A recently developed model based on the structural-elastic properties of molecules fits our data well,indicating that the bond formed by Al and GPlbαhas a catch-bond phenomenon in a certain interval of external forces,and a flex bond in other force intervals.In conclusion,A1-GPIbαbond will have a'slip-catch-slip'bond tendency.Our result provides a alte
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