The Structural Basis for Site-Specific Lysine-Acetylated Histone Recognition by the Bromodomains of the HUman Transcriptional Co-Activators PCAF and CBP
2rnx is a 2 chain structure with sequence from Atcc 18824 and Human. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
[KAT2B_HUMAN] Functions as a histone acetyltransferase (HAT) to promote transcriptional activation. Has significant histone acetyltransferase activity with core histones (H3 and H4), and also with nucleosome core particles. Also acetylates non-histone proteins, such as ACLY. Inhibits cell-cycle progression and counteracts the mitogenic activity of the adenoviral oncoprotein E1A. In case of HIV-1 infection, it is recruited by the viral protein Tat. Regulates Tat's transactivating activity and may help inducing chromatin remodeling of proviral genes.[1][2][3][4]
Evolutionary Conservation
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Publication Abstract from PubMed
Histone lysine acetylation is central to epigenetic control of gene transcription. Bromodomains of chromosomal proteins function as acetyl-lysine (Kac) binding domains. However, how bromodomains recognize site-specific histones remains unanswered. Here, we report three three-dimensional solution structures of the bromodomains of the human transcriptional coactivators CREB-binding protein (CBP) and p300/CBP-associated factor (PCAF) bound to peptides derived from histone acetylation sites at lysines 36 and 9 in H3, and lysine 20 in H4. From structural and biochemical binding analyses, we determine consensus histone recognition by the bromodomains of PCAF and CBP, which represent two different subgroups of the bromodomain family. Through bromodomain residues in the ZA and BC loops, PCAF prefers acetylation sites with a hydrophobic residue at (Kac+2) position and a positively charged or aromatic residue at (Kac+3), whereas CBP favors bulky hydrophobic residues at (Kac+1) and (Kac+2), a positively charged residue at (Kac-1), and an aromatic residue at (Kac-2).
Structural basis of site-specific histone recognition by the bromodomains of human coactivators PCAF and CBP/p300.,Zeng L, Zhang Q, Gerona-Navarro G, Moshkina N, Zhou MM Structure. 2008 Apr;16(4):643-52. PMID:18400184[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
↑Yang XJ, Ogryzko VV, Nishikawa J, Howard BH, Nakatani Y. A p300/CBP-associated factor that competes with the adenoviral oncoprotein E1A. Nature. 1996 Jul 25;382(6589):319-24. PMID:8684459 doi:10.1038/382319a0
↑Zhang W, Bieker JJ. Acetylation and modulation of erythroid Kruppel-like factor (EKLF) activity by interaction with histone acetyltransferases. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9855-60. PMID:9707565
↑Martinez-Balbas MA, Bauer UM, Nielsen SJ, Brehm A, Kouzarides T. Regulation of E2F1 activity by acetylation. EMBO J. 2000 Feb 15;19(4):662-71. PMID:10675335 doi:10.1093/emboj/19.4.662
↑Lin R, Tao R, Gao X, Li T, Zhou X, Guan KL, Xiong Y, Lei QY. Acetylation stabilizes ATP-citrate lyase to promote lipid biosynthesis and tumor growth. Mol Cell. 2013 Aug 22;51(4):506-18. doi: 10.1016/j.molcel.2013.07.002. Epub 2013 , Aug 8. PMID:23932781 doi:https://dx.doi.org/10.1016/j.molcel.2013.07.002
↑Zeng L, Zhang Q, Gerona-Navarro G, Moshkina N, Zhou MM. Structural basis of site-specific histone recognition by the bromodomains of human coactivators PCAF and CBP/p300. Structure. 2008 Apr;16(4):643-52. PMID:18400184 doi:10.1016/j.str.2008.01.010
