Understanding apparent DNA flexibility enhancement by HU and HMGB architectural proteins

Luke Czapla, Justin P. Peters, Emily M. Rueter, Wilma K. Olson, L James Maher III

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Understanding and predicting the mechanical properties of protein/DNA complexes are challenging problems in biophysics. Certain architectural proteins bind DNA without sequence specificity and strongly distort the double helix. These proteins rapidly bind and unbind, seemingly enhancing the flexibility of DNA as measured by cyclization kinetics. The ability of architectural proteins to overcome DNA stiffness has important biological consequences, but the detailed mechanism of apparent DNA flexibility enhancement by these proteins has not been clear. Here, we apply a novel Monte Carlo approach that incorporates the precise effects of protein on DNA structure to interpret new experimental data for the bacterial histone-like HU protein and two eukaryotic high-mobility group class B (HMGB) proteins binding to ∼ 200-bp DNA molecules. These data (experimental measurement of protein-induced increase in DNA cyclization) are compared with simulated cyclization propensities to deduce the global structure and binding characteristics of the closed protein/DNA assemblies. The simulations account for all observed (chain length and concentration dependent) effects of protein on DNA behavior, including how the experimental cyclization maxima, observed at DNA lengths that are not an integral helical repeat, reflect the deformation of DNA by the architectural proteins and how random DNA binding by different proteins enhances DNA cyclization to different levels. This combination of experiment and simulation provides a powerful new approach to resolve a long-standing problem in the biophysics of protein/DNA interactions.

Original languageEnglish (US)
Pages (from-to)278-289
Number of pages12
JournalJournal of Molecular Biology
Volume409
Issue number2
DOIs
StatePublished - Jun 3 2011

Fingerprint

DNA
Cyclization
Proteins
Biophysics
IgA receptor
DNA-Binding Proteins
Protein Binding
Histones

Keywords

  • bovine serum albumin
  • BSA
  • high-mobility group B
  • HMGB
  • National Institutes of Health
  • NIH
  • PDB
  • Protein Data Bank

ASJC Scopus subject areas

  • Molecular Biology

Cite this

Understanding apparent DNA flexibility enhancement by HU and HMGB architectural proteins. / Czapla, Luke; Peters, Justin P.; Rueter, Emily M.; Olson, Wilma K.; Maher III, L James.

In: Journal of Molecular Biology, Vol. 409, No. 2, 03.06.2011, p. 278-289.

Research output: Contribution to journalArticle

Czapla, Luke ; Peters, Justin P. ; Rueter, Emily M. ; Olson, Wilma K. ; Maher III, L James. / Understanding apparent DNA flexibility enhancement by HU and HMGB architectural proteins. In: Journal of Molecular Biology. 2011 ; Vol. 409, No. 2. pp. 278-289.
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