Structural Basis of Novel Interactions Between the Small-GTPase and GDI-like Domains in Prokaryotic FeoB Iron Transporter

Summary The FeoB family proteins are widely distributed prokaryotic membrane proteins involved in Fe 2+ uptake. FeoB consists of N-terminal cytosolic and C-terminal transmembrane domains. The N-terminal region of the cytosolic domain is homologous to small GTPase (G) proteins and is considered to regulate Fe 2+ uptake. The spacer region connecting the G and TM domains reportedly functions as a GDP dissociation inhibitor (GDI)–like domain that stabilizes the GDP-binding state. However, the function of the G and GDI-like domains in iron uptake remains unclear. Here, we report the structural and functional analyses of the FeoB cytosolic domain from Thermotoga maritima. The structure-based mutational analysis indicated that the interaction between the G and GDI-like domains is important for both the GDI and Fe 2+ uptake activities. On the basis of these results, we propose a regulatory mechanism of Fe 2+ uptake.