Abstract
SopB is a type III secreted Salmonella effector protein with phosphoinositide phosphatase activity and a distinct GTPase binding domain. The latter interacts with host Cdc42, an essential Rho GTPase that regulates critical events in eukaryotic cytoskeleton organization and membrane trafficking. Structural and biochemical analysis of the SopB GTPase binding domain in complex with Cdc42 shows for the first time that SopB structurally and functionally mimics a host guanine nucleotide dissociation inhibitor (GDI) by contacting key residues in the regulatory switch regions of Cdc42 and slowing Cdc42 nucleotide exchange.
Highlights
Salmonella effector protein SopB binds host Rho GTPase Cdc42
Rho GTPases regulate a multitude of cellular processes such as cytoskeleton organization, cell division, and cell motility [36]
Members of the Rho GTPase family are low molecular weight proteins containing two flexible regulatory switch regions, termed switch I and II, that bind and hydrolyze GTP. They function as molecular switches, which are active in the GTP-bound state and inactive in the GDP-bound state [36]
Summary
Salmonella effector protein SopB binds host Rho GTPase Cdc. Results: Structural characterization of SopB with Cdc reveals that SopB contains a CRIB-like motif and contacts Cdc switch regions. SopB is a type III secreted Salmonella effector protein with phosphoinositide phosphatase activity and a distinct GTPase binding domain The latter interacts with host Cdc, an essential Rho GTPase that regulates critical events in eukaryotic cytoskeleton organization and membrane trafficking. This structure shows that SopB contacts Cdc by mimicking a eukaryotic CRIB (for Cdc and Rac-interactive binding)-like motif, which was previously unidentified due to a lack of sequence conservation This is the first time a bacterial effector protein has been shown to contact a Rho GTPase through a CRIB-like motif. Our structure shows that SopB mimics key interactions between Cdc and host guanine dissociation inhibitor (GDI), a regulatory protein that sequesters Cdc in the inactive state by preventing exchange of GDP for GTP. In vitro nucleotide exchange assays confirm that the N-terminal domain of SopB slows intrinsic Cdc nucleotide exchange as well as Cdc nucleotide exchange catalyzed by the Salmonella GEF, SopE
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