title: Structure and function of the phosphothreonine-specific FHA domain.
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.
authors.affiliation: Biophysics Program, Ohio State University, Columbus, OH 43210, USA.
authors.forename: Anjali
authors.initials: A
authors.lastname: Mahajan
authors.forename: Chunhua
authors.initials: C
authors.lastname: Yuan
authors.forename: Hyun
authors.initials: H
authors.lastname: Lee
authors.forename: Eric S-W
authors.initials: ES
authors.lastname: Chen
authors.forename: Pei-Yu
authors.initials: PY
authors.lastname: Wu
authors.forename: Ming-Daw
authors.initials: MD
authors.lastname: Tsai
mesh_terms: D001665:Binding Sites; D051858:Forkhead Transcription Factors / Q000737:chemistry / Q000378:metabolism*; D010769:Phosphothreonine / Q000378:metabolism*; D017434:Protein Structure, Tertiary
chemical_list: D051858:Forkhead Transcription Factors; D010769:Phosphothreonine