Structural Properties of the Promiscuous VP16 Activation Domain

• DOI: 10.1021/bi0482912
• Publication Date: 2005-01-18T05:34:27Z
• Authors: Hendrik R. A. Jonker; Rainer W. Wechsel...; Rolf Boelens; Gert E. Folkers; Rob Kaptein
• Keywords: Cooperative binding; Intrinsically Disordered Proteins; Cooperativity; Docking (animal)

Herpes simplex virion protein 16 (VP16) contains two strong activation regions that can independently and cooperatively activate transcription in vivo. We have identified the residues involved interaction with human transcriptional coactivator positive cofactor 4 (PC4) general factor TFIIB. NMR biochemical experiments revealed both VP16 are required for undergo a conformational transition from random coil to α-helix upon binding its target PC4. The is strongly electrostatically driven PC4 enhanced by presence of amino-terminal domain. propose models core domains TFIIB based on independent docking approaches using chemical shift changes observed titration experiments. consistent results site-directed mutagenesis provide an explanation contribution acidic hydrophobic VP16. Both intrinsically unstructured attracted their partner electrostatic interactions, adopt α-helical conformation around important residues. showed multiple distinct surfaces various partners, providing promiscuous properties, cooperativity, high activity this