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Updated: Jun 26, 2026

Fluorescence Assays for the Study of Mycobacterium tuberculosis Interaction with the Immune Receptor SLAMF1
Published on: February 28, 2025
The FHA-containing protein GarA acts as a phosphorylation-dependent molecular switch in mycobacterial signaling
Patrick England1, Annemarie Wehenkel, Sonia Martins
1Institut Pasteur, Unité de Biochimie Structurale, & CNRS URA 2185, 25 rue du Docteur. Roux, F-75724 Paris, France.
Abstract:
Fork-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.
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