Dynamic and Structural Characterization of a Bacterial FHA Protein Reveals a New Autoinhibition Mechanism

• DOI: 10.1016/j.str.2009.02.012
• Publication Date: 2009-04-15T08:15:23Z
• Authors: Philippe Barthe; Christian Roumestand; Marc J. Canova; Laurent Kremer; Corinne Hurard; Virginie Molle; Martin Cohen-Gonsaud
• Keywords: Characterization

The OdhI protein is key regulator of the TCA cycle in Corynebacterium glutamicum. This highly conserved protein is found in GC rich Gram-positive bacteria (e.g., the pathogenic Mycobacterium tuberculosis). The unphosphorylated form of OdhI inhibits the OdhA protein, a key enzyme of the TCA cycle, whereas the phosphorylated form is inactive. OdhI is predicted to be mainly a single FHA domain, a module that mediates protein-protein interaction through binding of phosphothreonine peptides, with a disordered N-terminal extension substrate of the serine/threonine protein kinases. In this study, we solved the solution structure of the unphosphorylated and phosphorylated isoforms of the protein. We observed a major conformational change between the two forms characterized by the binding of the phosphorylated N-terminal part of the protein to its own FHA domain, consequently inhibiting it. This structural observation corresponds to a new autoinhibition mechanism described for a FHA domain protein.