The Heparan Sulfate Binding Sequence of Interferon-γ Increased the On Rate of the Interferon-γ-Interferon-γ Receptor Complex Formation

摘要: Interferon-gamma (IFNgamma), in common with a number of growth factors, binds both to heparan sulfate or heparin-related molecules and specific high affinity receptor (IFNgammaR). Using surface plasmon resonance technology, kinetic analysis the IFNgamma. IFNgammaR complex formation was performed extracellular part immobilized on sensor chip. At chip surface, IFNgamma bound by two an nanomolar range (0.68 nM). This binding characterized important rate, kon = 7.3 x 10(6) M-1.s-1, off koff 5 10(-3).s-1. assay used investigate possible role heparin IFNgamma.IFNgammaR formation. In contrast factors for which is usually required interaction, we found this study that displayed strongly reduced its receptor. consistent fact cluster basic amino acids (KTGKRKR, called C1 domain) carboxyl-terminal sequence cytokine involved recognition. To understand how single domain could be implicated discrete functions (i.e. IFNgammaR), also analyzed detailed manner binding. forms IFNgamma, carboxyl terminus truncations defined regions sequence, functioned increasing rate reaction but not otherwise stability complex. Interactions between increased association either encounters favoring productive collisions. The mechanisms regulates activity may thus include control selective protease cleavage events, directly affect activity, ability modulate interaction via competitive domain.