2phe
From Proteopedia
Model for VP16 binding to PC4
Structural highlights
Function[TCP4_HUMAN] General coactivator that functions cooperatively with TAFs and mediates functional interactions between upstream activators and the general transcriptional machinery. May be involved in stabilizing the multiprotein transcription complex. Binds single-stranded DNA. Also binds, in vitro, non-specifically to double-stranded DNA (ds DNA).[1] [2] [3] [4] [5] [6] [7] [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 PubMedHerpes 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[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Hhv-1 | Human | Large Structures | Boelens, R | Folkers, G E | Jonker, H R.A | Kaptein, R | Wechselberger, R W | Activator | Cofactor | Pc4 | Transcription | Vp16
