Research ArticleMicrobiology

A Phosphorylated Pseudokinase Complex Controls Cell Wall Synthesis in Mycobacteria

Science Signaling  24 Jan 2012:
Vol. 5, Issue 208, pp. ra7
DOI: 10.1126/scisignal.2002525

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The Bacterial Cell Wall Construction Foremen

The bacterial peptidoglycan cell wall is essential for viability and pathogenesis and represents the target of many antibacterial drugs. In Mycobacterium tuberculosis, which causes tuberculosis, the transmembrane protein MviN is required for peptidoglycan synthesis and contains a kinase-like domain not found in the orthologous proteins of other bacteria. Structural analysis by Gee et al. revealed that, although the kinase homology domain adopted a conserved kinase fold, the protein was an inactive pseudokinase. Biochemical analysis showed that this pseudokinase was a substrate for the Ser-Thr kinase PknB, which is activated by peptidoglycan fragments. Structural and biochemical analysis revealed a high-affinity interaction between the FHA domain–containing protein FhaA and phosphorylated MviN. Conditional depletion or overexpression experiments in vivo suggested that PknB-mediated phosphorylation of the pseudokinase domain of MviN enabled the inhibition of MviN by FhaA. Thus, this protein kinase–pseudokinase–FHA cascade appears to serve as a homeostatic regulator of cell wall metabolism.