2phg
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(New page: 200px<br /> <applet load="2phg" size="450" color="white" frame="true" align="right" spinBox="true" caption="2phg" /> '''Model for VP16 binding to TFIIB'''<br /> =...)
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Revision as of 21:17, 12 November 2007
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Model for VP16 binding to TFIIB
Overview
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.
About this Structure
2PHG is a Protein complex structure of sequences from Homo sapiens and Human herpesvirus 4. Full crystallographic information is available from OCA.
Reference
Structural properties of the promiscuous VP16 activation domain., Jonker HR, Wechselberger RW, Boelens R, Folkers GE, Kaptein R, Biochemistry. 2005 Jan 25;44(3):827-39. PMID:15654739
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