InterPro domain: IPR007889

The psq-type HTH domain is a DNA-binding, helix-turn-helix (HTH) domain ofabout 50 amino acids present in eukaryotic proteins of the Pipsqueak family.This family is named after the Drosophila pipsqueak protein, containing aDNA-binding domain that consists of four tandem repeats of the psq motif [ 1 ].Proteins of the Pipsqueak family occur in vertebrates, insects, nematodes, andfungi.

Three subgroups of the family have been described: BTB, E93 and CENP-B.Pipsqueak and the other proteins of the BTB group (Broad-Complex, Tramtrack,Bric a brac) contain a BTB protein-protein interaction domain in the N-terminal part, and the psq-type HTH domain(s) occur in the C-terminal part. Many BTB proteins are transcriptional regulators and the psq-type HTH domain binds DNA. The Drosophila cell death regulating protein E93 and human orthologs form the second subgroup and can contain the psq-type HTH at varying positions. The human centromere protein B (CENP-B) and the other members of the CENP-B group contain a psq-type DNA-binding domain in the N-terminal part and often a dimerisation domain in the C-terminal part. The CENP-B group includes fungal transposases that, however, lack the N-terminal extremity of the psq-type HTHdomain [ 2 ].

The structure of human CENP-B shows that the N-terminal part of the DNA binding domain is composed of three alpha-helices. The second and third helices connected via a turn comprise the helix-turn-helix motif. Helix 3 is termed the recognition helix as it binds the DNA major groove, like in other HTHs [ 3 ].

1. The pipsqueak protein of Drosophila melanogaster binds to GAGA sequences through a novel DNA-binding domain. J. Biol. Chem. 273, 28504-9
2. The Drosophila Pipsqueak protein defines a new family of helix-turn-helix DNA-binding proteins. Dev. Genes Evol. 212, 152-7
3. Crystal structure of the CENP-B protein-DNA complex: the DNA-binding domains of CENP-B induce kinks in the CENP-B box DNA. EMBO J. 20, 6612-8