CONSERVATION OF A PUTATIVE INHIBITORY DOMAIN IN THE GAL4 FAMILY MEMBERS

The GAL4 family members are fungal transcriptional activators composed of several functional domains: a characteristic cysteine-rich DNA-bin ding domain common to all members, a dimerization domain, various tran sactivation domains generally exhibiting a high acidic content and a h ighly variable central region supposed to be involved in regulation an d in effector recognition. We report here that the central region of t he GAL4 family members share eight conserved motifs embedded in a larg e functional domain of 225 up to 405 residues. This domain may also be present in four proteins belonging to another family of transcription al activators sharing a C2H2-type zinc finger. Analysis of the biochem ical data available on the well-studied GAL4 protein suggests that thi s domain may be involved in the regulation of the activity of the prot ein, particularly in an inhibitory function. This hypothesis is furthe r supported by deletion and site-directed mutagenesis experiments on o ther GAL4 family members. The mean secondary structure prediction perf ormed on the eight motifs strongly suggests that the inhibitory activi ty may be mediated by hydrophobic interactions linked to the presence of amphipathic alpha-helices.