Critical structural elements of the VP16 transcriptional activation domain.

Virion protein 16 (VP16) of herpes simplex virus type 1 contains an acidic transcriptional activation domain. Missense mutations within this domain have provided insights into the structural elements critical for its function. Net negative charge contributed to, but was not sufficient for, transcriptional activation by VP16. A putative amphipathic alpha helix did not appear to be an important structural component of the activation domain. A phenylalanine residue at position 442 was exquisitely sensitive to mutation. Transcriptional activators of several classes contain hydrophobic amino acids arranged in patterns resembling that of VP16. Therefore, the mechanism of transcriptional activation by VP16 and other proteins may involve both ionic and specific hydrophobic interactions with target molecules.