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Effect of Phosphorylation on the Structural Behaviour of Peptides Derived from the Intrinsically Disordered C‐Terminal Domain of Histone H1.0
Author(s) -
ChavesArquero Belén,
PérezCañadillas José M.,
Jiménez M. Angeles
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201905496
Subject(s) - histone h1 , phosphorylation , side chain , chemistry , peptide , structural motif , intrinsically disordered proteins , crystallography , stereochemistry , protein structure , biophysics , histone , biochemistry , biology , polymer , dna , organic chemistry
To investigate the structural impact of phosphorylation on the human histone H1.0 C‐terminal domain, we performed NMR structural studies of model peptides containing a single phosphorylation site: T 118 ‐H1.0 (T 118 PKK motif) and T 140 ‐H1.0 (T 140 PVK motif). Both model peptides are mainly disordered in aqueous solution in their non‐phosphorylated and phosphorylated forms, but become structured in the presence of trifluoroethanol. The peptides T 118 ‐H1.0 and pT 118 ‐H1.0 contain two helical regions, a long amphipathic α helix spanning residues 104–115 and a short α/3 10 helix (residues 119–123), that are almost perpendicular in T 118 ‐H1.0 but have a poorly defined orientation in pT 118 ‐H1.0. Peptides T 140 ‐H1.0 and pT 140 ‐H1.0 form very similar α helices between residues 141–147. The TPKK and TPVK motifs show the same backbone conformation, but differ in their side‐chain contacts; the Thr and pThr side chains interact with the i +2 Lys side chain in the TPKK motif, and with the i +3 Lys side chain in the TPVK motif. The pT phosphate group in pT 118 ‐H1.0 and pT 140 ‐H1.0 has p K a values below the intrinsic values, which can be explained by non‐specific charge–charge interactions with nearby Lys. The non‐polar Val in the TPVK motif accounts for the pT 140 p K a being closer to the intrinsic p K a value than the pT 118 p K a . Altogether, these results validate that minimalist strategies using model peptides can provide structural details difficult to obtain in short‐lived intrinsically disordered proteins and domains.