Faculty Publications

Understanding Apparent DNA Flexibility Enhancement by HU and HMGB Architectural Proteins

Document Type

Article

Keywords

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

Journal/Book/Conference Title

Journal of Molecular Biology

Volume

409

Issue

2

First Page

278

Last Page

289

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. © 2011 Elsevier Ltd. All rights reserved.

Department

Department of Chemistry and Biochemistry

Original Publication Date

6-3-2011

DOI of published version

10.1016/j.jmb.2011.03.050

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