Abstract

The forkhead-associated FHA domain is a phosphopeptide-binding domain first identified in a group of forkhead transcription factors (Hofmann and Bucher, 1995). FHA are small domains (<100 aminoacids) which form a sandwich of two antiparallel beta sheets (Walker et al., 2000). They are present in a wide variety of proteins from both prokaryotes and eukaryotes (Walker et al., 2000). The existence of FHA domains in a wide variety of proteins means they are involved in diverse cellular functions including signal transduction and vesicular transport. In plants, FHA domains participate in the regulation of receptor-like protein kinase signalling pathways (Doren et al., 2003). There are many nuclear FHA-domain containing proteins: these have a variety of roles involved in cell-cycle checkpoint control, DNA repair, signal transduction, transcriptional regulation, and pre-mRNA splicing. Some of the FHA domain containing proteins are present in the plasma membrane. While FHAs bind to phosphothreonine motifs, BRCT domains recognize phosphoserine motifs in otherwise similar nuclear regulatory contexts. Although weak in vitro binding of phosphoserine and phosphotyrosine peptides has been observed, all high affinity interactions utilize phosphothreonine, which may be an essential requirement for the biological ligands. The optimal FHA domain binding sequence is a phosphothreonine peptide with pT+3 specificity (Li et al., 2003). So far there are two well characterised motifs TXX[ILV] and TXX[DE] - while TXXC and TXXA have been observed, they are not currently modelled in ELM. The TXXC linear motif forms part of a larger induced fit interaction with the FHA domain (Byeon et al.,2004). More variations among the FHA-binding motifs are expected to be found.