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Sci. Signal., 23 December 2008
Vol. 1, Issue 51, p. re12
[DOI: 10.1126/scisignal.151re12]

REVIEWS

Structure and Function of the Phosphothreonine-Specific FHA Domain

Anjali Mahajan1, Chunhua Yuan2, Hyun Lee1,3, Eric S.-W. Chen3,4,5, Pei-Yu Wu5, and Ming-Daw Tsai1,2,3,4,5*

1 Biophysics Program, Ohio State University, Columbus, OH 43210, USA.
2 Campus Chemical Instrument Center, Ohio State University, Columbus, OH 43210, USA.
3 Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
4 Institute of Biochemical Science, National Taiwan University, Taipei 10617, Taiwan.
5 Institute of Biological Chemistry, Academia Sinica, Taipei 115, Taiwan.

Abstract: The forkhead-associated (FHA) domain is the only known phosphoprotein-binding domain that specifically recognizes phosphothreonine (pThr) residues, distinguishing them from phosphoserine (pSer) residues. In contrast to its very strict specificity toward pThr, the FHA domain recognizes very diverse patterns in the residues surrounding the pThr residue. For example, the FHA domain of Ki67, a protein associated with cellular proliferation, binds to an extended target surface involving residues remote from the pThr, whereas the FHA domain of Dun1, a DNA damage–response kinase, specifically recognizes a doubly phosphorylated Thr-Gln (TQ) cluster by virtue of its possessing two pThr-binding sites. The FHA domain exists in various proteins with diverse functions and is particularly prevalent among proteins involved in the DNA damage response. Despite a very short history, a number of unique structural and functional properties of the FHA domain have been uncovered. This review highlights the diversity of biological functions of the FHA domain–containing proteins and the structural bases for the novel binding specificities and multiple binding modes of FHA domains.

* Corresponding author. E-mail: mdtsai{at}gate.sinica.edu.tw

Citation: A. Mahajan, C. Yuan, H. Lee, E. S.-W. Chen, P.-Y. Wu, M.-D. Tsai, Structure and Function of the Phosphothreonine-Specific FHA Domain. Sci. Signal. 1, re12 (2008).

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