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[求助]
求翻译一段英语
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| Loop Dynamics of the Extracellular Domain of Human Tissue Factor and Activation of Factor VIIaIn the crystal structure of the complex between the soluble extracellular domain of tissue factor (sTF) and activesite-inhibited VIIa, residues 91 and 92 in the Pro79-Pro92 loop of sTF interact with the catalytic domain of VIIa. It is not known,however, whether this loop has a role in allosteric activation of VIIa. Time-resolved fluorescence anisotropy measurements ofprobes covalently bound to sTF mutants E84C and T121C show that binding uninhibited Factor VIIa affects segmental motionsin sTF. Glu84 resides in the Pro79-Pro92 loop, and Thr121 resides in the turn between the first and second antiparallel b-strands ofthe sTF subdomain that interacts with the Gla and EGF1 domains of VIIa; neither Glu84 nor Thr121 makes direct contact with VIIa.Probes bound to T121C report limited segmental flexibility in free sTF, which is lost after VIIa binding. Probes bound to E84Creport substantial segmental flexibility in the Pro79-Pro92 loop in free sTF, which is greatly reduced after VIIa binding. Thus,VIIa binding reduces dynamic motions in sTF. In particular, the decrease in the Pro79-Pro92 loop motions indicates that loopentropy has a role in the thermodynamics of the protein-protein interactions involved in allosteric control of VIIa activation. |
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