Taxonomic distribution of proteins containing Alpha_TIF domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing Alpha_TIF domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Structural properties of the promiscuous VP16 activation domain.

Jonker HR, Wechselberger RW, Boelens R, Folkers GE, Kaptein R
Biochemistry. 2005; 44: 827-39

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

The herpes simplex virus VP16-induced complex: the makings of a regulatory switch.

Wysocka J, Herr W
Trends Biochem Sci. 2003; 28: 294-304

When herpes simplex virus (HSV) infects human cells, it is able to enter two modes of infection: lytic and latent. A key activator of lytic infection is a virion protein called VP16, which, upon infection of a permissive cell, forms a transcriptional regulatory complex with two cellular proteins - the POU-domain transcription factor Oct-1 and the cell-proliferation factor HCF-1 - to activate transcription of the first set of expressed viral genes. This regulatory complex, called the VP16-induced complex, reveals mechanisms of combinatorial control of transcription. The activities of Oct-1 and HCF-1 - two important regulators of cellular gene expression and proliferation - illuminate strategies by which HSV might coexist with its host.

Nucleotide and deduced amino acid sequences of the gene encoding virion protein 16 of herpes simplex virus type 2.

Cress A, Triezenberg SJ
Gene. 1991; 103: 235-8

A virion protein (VP16) of herpes simplex virus (HSV) activates transcription of viral immediate-early genes. We have determined the nucleotide sequence of the virion activator gene from HSV-2, which we term VP16-2. Comparison of the deduced amino acid sequences of the HSV-1 and HSV-2 homologs shows that the VP16-2 gene product retains features determined to be important for transcriptional activation by VP16.