2PHG
Model for VP16 binding to TFIIB
Summary for 2PHG
| Entry DOI | 10.2210/pdb2phg/pdb |
| Related | 1TFB 2phe |
| Descriptor | Transcription initiation factor IIB, Alpha trans-inducing protein (2 entities in total) |
| Functional Keywords | tf2b, vp16, transcription, activator |
| Biological source | Homo sapiens (human) More |
| Cellular location | Nucleus: Q00403 Virion tegument (By similarity): P06492 |
| Total number of polymer chains | 2 |
| Total formula weight | 25901.95 |
| Authors | Jonker, H.R.A.,Wechselberger, R.W.,Boelens, R.,Folkers, G.E.,Kaptein, R. (deposition date: 2007-04-11, release date: 2007-04-24, Last modification date: 2024-05-22) |
| Primary citation | Jonker, H.R.A.,Wechselberger, R.W.,Boelens, R.,Folkers, G.E.,Kaptein, R. Structural Properties of the Promiscuous VP16 Activation Domain Biochemistry, 44:827-839, 2005 Cited by PubMed Abstract: 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. PubMed: 15654739DOI: 10.1021/bi0482912 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
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