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FEBS Lett. 2009 Jan 22;583(2):301-7. doi: 10.1016/j.febslet.2008.12.036. Epub 2008 Dec 27.

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

Author information

1
Institut 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.

PMID:
19114043
DOI:
10.1016/j.febslet.2008.12.036
[Indexed for MEDLINE]
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