The structure of the full catalytic cycle of Vibrio cholerae NFeoB

Abstract

The acquisition of iron is critical for the survival and the virulence of numerous infectious pathogens, and most bacteria acquire ferrous iron (Fe2+) by utilizing the ferrous iron transport (Feo) system. FeoB is the main component of this system, and its function is regulated by the soluble cytosolic domain, termed NFeoB. We have recently begun to define the structure and the mechanism of the Feo system from the bacterium Vibrio cholerae, the causative agent of the disease cholera. However, major structural gaps in our understanding of the nucleotide-promiscuous V. cholerae NFeoB still exist. In this work, we have determined several new X-ray crystal structures that reveal distinct snapshots of the VcNFeoB domain in uncommon and unprecedented states, ultimately illuminating the full catalytic cycle of this NTPase. This work reveals important functional features of VcNFeoB that may be leveraged and ultimately targeted to prevent the infectivity and the spread of cholera. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=187 SRC="FIGDIR/small/680749v1_ufig1.gif" ALT="Figure 1"> View larger version (75K): org.highwire.dtl.DTLVardef@180652org.highwire.dtl.DTLVardef@146f5a4org.highwire.dtl.DTLVardef@1a913e0org.highwire.dtl.DTLVardef@1581586_HPS_FORMAT_FIGEXP M_FIG C_FIG