• Севастьян Олегович Рабдано
  • M. Shannon
  • Сергей Александрович Измайлов
  • N. Gonzalez Salguero
  • M. Zandian
  • Rudra N. Purusottam
  • M. Poirier
  • Christopher Jaroniec
  • Николай Русланович Скрынников

The interaction of positively charged N-terminal histone tails with nucleosomal DNA plays an important role in chromatin assembly and regulation, modulating their susceptibility to post-translational modifications and recognition by chromatin-binding proteins. Here, we report residue-specific 15N NMR relaxation rates for histone H4 tails in reconstituted nucleosomes. These data indicate that H4 tails are strongly dynamically disordered, albeit with reduced conformational flexibility compared to a free peptide with the same sequence. Remarkably, the NMR observables were successfully reproduced in a 2-μs MD trajectory of the nucleosome. This is an important step toward resolving an apparent inconsistency where prior simulations were generally at odds with experimental evidence on conformational dynamics of histone tails. Our findings indicate that histone H4 tails engage in a fuzzy interaction with nucleosomal DNA, underpinned by a variable pattern of short-lived salt bridges and hydrogen bonds, which persists at low ionic strength (0–100 mM NaCl).

Original languageEnglish
Pages (from-to)6480-6487
Number of pages8
JournalAngewandte Chemie - International Edition
Issue number12
Early online date31 Jan 2021
StatePublished - 15 Mar 2021

    Scopus subject areas

  • Chemistry(all)
  • Catalysis

    Research areas

  • NMR spectroscopy, fuzzy protein–DNA interactions, histone tails, molecular dynamics, nucleosome, DNA/chemistry, Histones/chemistry, Nucleosomes/chemistry, WATER MODEL, SIDE-CHAINS, CORE PARTICLES, INTRINSICALLY DISORDERED PROTEINS, N-TERMINAL PEPTIDES, DNA interactions, H4-K16 ACETYLATION, STRUCTURAL DISORDER, DYNAMICS, fuzzy protein&#8211, FORCE-FIELD, SALT BRIDGES

ID: 73378489