Phosphorylation of Serine Induces Lysine pKₐ Increases in Histone N-Termini and Signaling for Acetylation. Transcription Implications
2018
Manning, Lois R. | Manning, James M.
The mild acetylating agent, methyl acetyl phosphate, is used to estimate the pKₐ values of some of the amine groups in peptides with sequences corresponding to a segment of the N-terminal tail of histone H4. When Ser-1 is not phosphorylated, the Lys ε amines have pKₐ values in the range of 7.8–8.3, which are much lower than the currently assumed values. When Ser-1 is phosphorylated, the pKₐ values of these Lys amines are elevated to the range of 8.8–10.3, thus providing the rationale for reports that they are then better substrates for acetyltransferases. Thus, reversal of suppressed pKₐ values of Lys ε amines by Ser phosphorylation represents the basis for signaling in histone N-terminal tails to promote hyperacetylation, which is a hallmark of transcriptionally active euchromatin. In contrast, a state of hypoacetylation is present in the absence of phosphorylation as in transcriptionally inactive heterochromatin. A novel approach for estimating pKₐ values based on a linkage between the Henderson–Hasselbalch and Michaelis–Menten equations indicates that the pKₐ values of the Lys ε amines in H3 and H4 N-terminal tails have a highly variable charge gradient dependent on the location and proximity to the phosphorylation site.
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