Human geranylgeranyl diphosphate synthase is an octamer in solution

A recombinant geranylgeranyl diphosphate synthase (GGPS) was analysed to be a mixture of octamer, hexamer and dimer by gel filtration using a Superdex 200 column followed by the blue native polyacrylamide gel electrophoresis. The hexamer and dimer were each converted to an octamer by treating with dithiothreitol (DTT). When the recombinant GGPS was preliminarily treated with DTT and similarly analysed, octamer was predominantly detected with a trace amount of hexamer. The octameric form of GGPS was also supported by the cross-linking experiments with bis(sulfosuccinimidyl) suberate. The GGPS in an octameric form was active with a combination of farnesyl diphosphate and [1-(14)C]isopentenyl diphosphate. These results indicate that the active form of GGPS in the solution is an octamer rather than hexamer or dimer.