The FHA-containing protein GarA acts as a phosphorylation-dependent molecular switch in mycobacterial signaling.
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.
England
Patrick
P
Institut Pasteur, Unité de Biochimie Structurale, & CNRS URA 2185, 25 rue du Docteur. Roux, F-75724 Paris, France.
Wehenkel
Annemarie
A
Martins
Sonia
S
Hoos
Sylviane
S
André-Leroux
Gwénaëlle
G
Villarino
Andrea
A
Alzari
Pedro M
PM
D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism*; D051858:Forkhead Transcription Factors / Q000737:chemistry; D018698:Glutamic Acid / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D010766:Phosphorylation; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015398:Signal Transduction
D001426:Bacterial Proteins; D051858:Forkhead Transcription Factors; D018698:Glutamic Acid; D006003:Glycogen