Single-Molecule Observation Reveals Spontaneous Protein Dynamics in the Nucleosome

Jongseong Kim, Sijie Wei, Jaehyoun Lee, Hongjun Yue, Tae-hee Lee

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Structural dynamics of a protein molecule is often critical to its function. Single-molecule methods provide efficient ways to investigate protein dynamics, although it is very challenging to achieve a millisecond or higher temporal resolution. Here we report spontaneous structural dynamics of the histone protein core in the nucleosome based on a single-molecule method that can reveal submillisecond dynamics by combining maximum likelihood estimation and fluorescence correlation spectroscopy. The nucleosome, comprising â147 bp DNA and an octameric histone protein core consisting of H2A, H2B, H3, and H4, is the fundamental packing unit of the eukaryotic genome. The nucleosome imposes a physical barrier that should be overcome during various DNA-templated processes. Structural fluctuation of the nucleosome in the histone core has been hypothesized to be required for nucleosome disassembly but has yet to be directly probed. Our results indicate that at 100 mM NaCl the histone H2A-H2B dimer dissociates from the histone core transiently once every 3.6 ± 0.6 ms and returns to its position within 2.0 ± 0.3 ms. We also found that the motion is facilitated upon H3K56 acetylation and inhibited upon replacing H2A with H2A.Z. These results provide the first direct examples of how a localized post-translational modification or an epigenetic variation affects the kinetic and thermodynamic stabilities of a macromolecular protein complex, which may directly contribute to its functions.

Original languageEnglish (US)
Pages (from-to)8925-8931
Number of pages7
JournalJournal of Physical Chemistry B
Volume120
Issue number34
DOIs
StatePublished - Sep 1 2016

Fingerprint

Nucleosomes
Histones
proteins
Proteins
Molecules
dynamic structural analysis
Structural dynamics
molecules
DNA
deoxyribonucleic acid
acetylation
Multiprotein Complexes
Acetylation
genome
Maximum likelihood estimation
temporal resolution
Dimers
Thermodynamic stability
Genes
Fluorescence

All Science Journal Classification (ASJC) codes

  • Physical and Theoretical Chemistry
  • Surfaces, Coatings and Films
  • Materials Chemistry

Cite this

Kim, Jongseong ; Wei, Sijie ; Lee, Jaehyoun ; Yue, Hongjun ; Lee, Tae-hee. / Single-Molecule Observation Reveals Spontaneous Protein Dynamics in the Nucleosome. In: Journal of Physical Chemistry B. 2016 ; Vol. 120, No. 34. pp. 8925-8931.
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Single-Molecule Observation Reveals Spontaneous Protein Dynamics in the Nucleosome. / Kim, Jongseong; Wei, Sijie; Lee, Jaehyoun; Yue, Hongjun; Lee, Tae-hee.

In: Journal of Physical Chemistry B, Vol. 120, No. 34, 01.09.2016, p. 8925-8931.

Research output: Contribution to journalArticle

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