| 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]
Publication Abstract from PubMed
PC4, a well-known general transcription cofactor, has multiple functions in transcription and DNA repair. Residue W89, is engaged in stacking interactions with DNA in PC4, but substituted by tyrosine in some PC4 orthologous proteins. In order to understand the consequences and reveal the molecular details of this substitution we have determined the crystal structures of the PC4 orthologue MoSub1 and a PC4 W89Y mutant in complex with DNA. In the structure of MoSub1-DNA complex, Y74 interacts directly with a single nucleotide of oligo DNA. By comparison, the equivalent residue, W89 in wild type PC4 interacts with two nucleotides and the base of the second nucleotide has distinct orientation relative to that of the first one. A hydrophobic patch around W89 that favours interaction with two nucleotides is not formed in the PC4 W89Y mutant. Therefore, the change of the surface hydrophobicity around residue 89 results in a difference between the modes of DNA interaction. These results indicate that the conserved Y74 in MoSub1 or W89 in PC4, are not only key residues in making specific interactions with DNA but also required to determine the DNA binding mode of PC4 proteins.
Substitution of tryptophan 89 with tyrosine switches the DNA binding mode of PC4.,Huang J, Zhao Y, Liu H, Huang D, Cheng X, Zhao W, Taylor IA, Liu J, Peng YL Sci Rep. 2015 Mar 5;5:8789. doi: 10.1038/srep08789. PMID:25739870[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kretzschmar M, Kaiser K, Lottspeich F, Meisterernst M. A novel mediator of class II gene transcription with homology to viral immediate-early transcriptional regulators. Cell. 1994 Aug 12;78(3):525-34. PMID:8062392
- ↑ Ge H, Roeder RG. Purification, cloning, and characterization of a human coactivator, PC4, that mediates transcriptional activation of class II genes. Cell. 1994 Aug 12;78(3):513-23. PMID:8062391
- ↑ Kaiser K, Stelzer G, Meisterernst M. The coactivator p15 (PC4) initiates transcriptional activation during TFIIA-TFIID-promoter complex formation. EMBO J. 1995 Jul 17;14(14):3520-7. PMID:7628453
- ↑ Malik S, Guermah M, Roeder RG. A dynamic model for PC4 coactivator function in RNA polymerase II transcription. Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2192-7. PMID:9482861
- ↑ Jonker HR, Wechselberger RW, Pinkse M, Kaptein R, Folkers GE. Gradual phosphorylation regulates PC4 coactivator function. FEBS J. 2006 Apr;273(7):1430-44. PMID:16689930 doi:http://dx.doi.org/10.1111/j.1742-4658.2006.05165.x
- ↑ Brandsen J, Werten S, van der Vliet PC, Meisterernst M, Kroon J, Gros P. C-terminal domain of transcription cofactor PC4 reveals dimeric ssDNA binding site. Nat Struct Biol. 1997 Nov;4(11):900-3. PMID:9360603
- ↑ Jonker HR, Wechselberger RW, Boelens R, Kaptein R, Folkers GE. The intrinsically unstructured domain of PC4 modulates the activity of the structured core through inter- and intramolecular interactions. Biochemistry. 2006 Apr 18;45(15):5067-81. PMID:16605275 doi:http://dx.doi.org/10.1021/bi052531b
- ↑ Huang J, Zhao Y, Liu H, Huang D, Cheng X, Zhao W, Taylor IA, Liu J, Peng YL. Substitution of tryptophan 89 with tyrosine switches the DNA binding mode of PC4. Sci Rep. 2015 Mar 5;5:8789. doi: 10.1038/srep08789. PMID:25739870 doi:http://dx.doi.org/10.1038/srep08789
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