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The FHA-containing protein GarA acts as a phosphorylation-dependent molecular switch in mycobacterial signaling

By Patrick England, Annemarie Wehenkel, Sonia Martins, Sylviane Hoos, Gwénaëlle André-Leroux, Andrea Villarino and Pedro M. Alzari

Abstract

AbstractFork-head associated (FHA) domains are widely found in bacteria, but their cellular functions remain unclear. Here, we focus on Mycobacterium tuberculosis GarA, an FHA-containing protein conserved in actinomycetes that is phosphorylated by different Ser/Thr protein kinases. Using various physicochemical approaches, we show that phosphorylation significantly stabilizes GarA, and that its FHA domain interacts strongly with the phosphorylated N-terminal extension. Altogether, our results indicate that phosphorylation triggers an intra-molecular protein closure, blocking the phosphothreonine-binding site and switching off the regulatory properties of GarA. The model can explain the reported functions of this mycobacterial protein as regulator of glycogen degradation and glutamate metabolism.Structured summary:MINT-6804218: GarA (uniprotkb:P64897) and GarA (uniprotkb:P64897) bind (MI:0407) by isothermal titration calorimetry (MI:0065

Publisher: Federation of European Biochemical Societies. Published by Elsevier B.V.
Year: 2009
DOI identifier: 10.1016/j.febslet.2008.12.036
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