Domain interactions in human plasminogen studied by proton NMR.

The NMR spectrum of miniplasminogen (V443-plasminogen) under conditions of acidic pH reveals a subset of particularly well-resolved resonances whose chemical shift values are closely similar to those of isolated kringle 5. The temperature dependence of the spectrum indicates that this set of resonances disappears in a single cooperative unfolding transition appropriate for kringle 5, whilst other broader resonances from the protease domain persist to higher temperature. These results provide evidence for significant structural and motional independence of the kringle and protease domains in spite of the short linker between these domains. The NMR spectrum of Glu1-plasminogen is closely similar to that of miniplasminogen under the same conditions. This suggests that the domain independence observed in miniplasminogen is maintained in the intact molecule.