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Sci. Signal., 24 March 2009
Vol. 2, Issue 63, p. ra12
[DOI: 10.1126/scisignal.2000212]


Editor's Summary

Newfound Independence
Protein-protein interactions are mediated by distinct regions, or domains, that exhibit varying degrees of specificity in their targets. The forkhead-associated (FHA) domain has the unusual property of distinguishing between phosphorylated serine (pSer) and phosphorylated threonine (pThr) residues in its interaction partners; whereas many other domains bind to both residues, FHA domains bind only to pThr. Or so we thought. Nott et al. performed structural and biochemical studies of Rv1827, a small protein from Mycobacterium tuberculosis, and found that it bound to and regulated the activities of three metabolic enzymes through its FHA domain; however, these interactions were independent of the phosphorylation status of the target proteins. In addition, phosphorylation of a Thr residue in its own amino terminus caused an intramolecular interaction that blocked the FHA domain of Rv1827 from binding to any of its targets. Together, these data expand our current understanding of the capabilities of the FHA domain, both in its binding capacity and in its potential regulatory functions.

Citation: T. J. Nott, G. Kelly, L. Stach, J. Li, S. Westcott, D. Patel, D. M. Hunt, S. Howell, R. S. Buxton, H. M. O’Hare, S. J. Smerdon, An Intramolecular Switch Regulates Phosphoindependent FHA Domain Interactions in Mycobacterium tuberculosis. Sci. Signal. 2, ra12 (2009).

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