title: The FHA-containing protein GarA acts as a phosphorylation-dependent molecular switch in mycobacterial signaling.
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.
authors.affiliation: Institut Pasteur, Unité de Biochimie Structurale, & CNRS URA 2185, 25 rue du Docteur. Roux, F-75724 Paris, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: England
authors.forename: Annemarie
authors.initials: A
authors.lastname: Wehenkel
authors.forename: Sonia
authors.initials: S
authors.lastname: Martins
authors.forename: Sylviane
authors.initials: S
authors.lastname: Hoos
authors.forename: Gwénaëlle
authors.initials: G
authors.lastname: André-Leroux
authors.forename: Andrea
authors.initials: A
authors.lastname: Villarino
authors.forename: Pedro M
authors.initials: PM
authors.lastname: Alzari
mesh_terms: 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
chemical_list: D001426:Bacterial Proteins; D051858:Forkhead Transcription Factors; D018698:Glutamic Acid; D006003:Glycogen