STRUCTURAL AND FUNCTIONAL ANALYSIS OF THE PHOSPHATASE AND PHOSPHOTRANSFERASE SALMONELLA OUTER PROTEIN B

Abstract

Salmonellosis, caused by Salmonella, is a global health issue primarily affecting the intestinal tract. SopB, a crucial effector protein, catalyzes the production of PI(3,4)P2 and PI(3,4,5)P3 from PI(4,5)P2, facilitating actin-dependent uptake and host cell survival. Initially thought to function solely as a phosphoinositide phosphatase, recent studies reveal that SopB also exhibits phosphoinositide phosphotransferase activity. While the phosphatase reaction requires water, phosphotransferase activity necessitates a phosphoinositide acceptor. It is hypothesized a tight plasma membrane association between the enzyme and substrate limits water access. The tight interaction allows for an accepting PI(4,5)P2 access to the phosphate group. Lipid-binding assays demonstrated SopB’s affinity for negatively charged lipids. N-terminal truncation mutants identified the minimal phosphotransferase catalytic domain. Key lysine and arginine residues may also facilitate phosphotransferase activity. These findings highlight the importance of distal polybasic regions for SopB’s plasma membrane localization and suggest future directions for developing inhibitors to combat antibiotic-resistant Salmonella strains.