Abstract
The G domain of a small monomeric GTPase Ras contains a nucleotide-binding pocket and a magnesium-binding site essential for the Ras function in cellular signaling. The G domain also has another (allosteric) ion-binding site on the rear surface of the G domain, which function is still unknown. In this paper, we detailed the effect of calcium and magnesium ions on stability of Ras bound to GDP, GTP, and GTP-mimic GppNHp. We revealed that the remote allosteric ion-binding site contributes very significantly to stability of Ras in the GDP-bound conformation, but nearly not at all - when Ras is bound to a GTP mimic. These findings highlight that further studies of the remote ion-binding site are warranted to reveal its role in the Ras function.
