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| | ==Model for VP16 binding to TFIIB== | | ==Model for VP16 binding to TFIIB== |
| - | <StructureSection load='2phg' size='340' side='right' caption='[[2phg]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> | + | <StructureSection load='2phg' size='340' side='right'caption='[[2phg]], [[NMR_Ensembles_of_Models | 10 NMR models]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2phg]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Hhv-1 Hhv-1] and [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PHG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2PHG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2phg]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Hhv-1 Hhv-1] and [https://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PHG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2PHG FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1tfb|1tfb]], [[2phe|2phe]]</td></tr> | + | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1tfb|1tfb]], [[2phe|2phe]]</div></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GTF2B, TF2B, TFIIB ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UL48 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10299 HHV-1])</td></tr> | + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">GTF2B, TF2B, TFIIB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), UL48 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10299 HHV-1])</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2phg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2phg OCA], [http://pdbe.org/2phg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2phg RCSB], [http://www.ebi.ac.uk/pdbsum/2phg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2phg ProSAT]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2phg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2phg OCA], [https://pdbe.org/2phg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2phg RCSB], [https://www.ebi.ac.uk/pdbsum/2phg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2phg ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/TF2B_HUMAN TF2B_HUMAN]] General factor that plays a major role in the activation of eukaryotic genes transcribed by RNA polymerase II. [[http://www.uniprot.org/uniprot/VP16_HHV11 VP16_HHV11]] Transcriptional activator of immediate-early (IE) gene products (alpha genes). Acts as a key activator of lytic infection by initiating the lytic program through the assembly of the transcriptional regulatory VP16-induced complex composed of VP16 and two cellular factors, HCFC1 and POU2F 1. VP16-induced complex represents a regulatory switch: when it is on, it promotes IE-gene expression and thus lytic infection, and when it is off, it limits IE-gene transcription favoring latent infection. May play a role in the aggregation of tegument proteins around nucleocapsids during virus morphogenesis. | + | [[https://www.uniprot.org/uniprot/TF2B_HUMAN TF2B_HUMAN]] General factor that plays a major role in the activation of eukaryotic genes transcribed by RNA polymerase II. [[https://www.uniprot.org/uniprot/VP16_HHV11 VP16_HHV11]] Transcriptional activator of immediate-early (IE) gene products (alpha genes). Acts as a key activator of lytic infection by initiating the lytic program through the assembly of the transcriptional regulatory VP16-induced complex composed of VP16 and two cellular factors, HCFC1 and POU2F 1. VP16-induced complex represents a regulatory switch: when it is on, it promotes IE-gene expression and thus lytic infection, and when it is off, it limits IE-gene transcription favoring latent infection. May play a role in the aggregation of tegument proteins around nucleocapsids during virus morphogenesis. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Hhv-1]] | | [[Category: Hhv-1]] |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Boelens, R]] | | [[Category: Boelens, R]] |
| | [[Category: Folkers, G E]] | | [[Category: Folkers, G E]] |
| Structural highlights
Function
[TF2B_HUMAN] General factor that plays a major role in the activation of eukaryotic genes transcribed by RNA polymerase II. [VP16_HHV11] Transcriptional activator of immediate-early (IE) gene products (alpha genes). Acts as a key activator of lytic infection by initiating the lytic program through the assembly of the transcriptional regulatory VP16-induced complex composed of VP16 and two cellular factors, HCFC1 and POU2F 1. VP16-induced complex represents a regulatory switch: when it is on, it promotes IE-gene expression and thus lytic infection, and when it is off, it limits IE-gene transcription favoring latent infection. May play a role in the aggregation of tegument proteins around nucleocapsids during virus morphogenesis.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Jonker HR, Wechselberger RW, Boelens R, Folkers GE, Kaptein R. Structural properties of the promiscuous VP16 activation domain. Biochemistry. 2005 Jan 25;44(3):827-39. PMID:15654739 doi:10.1021/bi0482912
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