Biophysical Society Thematic Meeting| Les Houches 2019

Multiscale Modeling of Chromatin: Bridging Experiment with Theory

Poster Abstracts

7-POS Board 7 DISORDERED PROTEINS ENABLE HISTONE CHAPERONING ON THE NUCLEOSOME Petur O. Heidarsson ; Davide Mercadante 1 ; Alessandro Borgia 1 ; Madeleine Borgia 1 ; Andrea Sottini 1 ; Sinan Kilic 2 ; Daniel Nettels 1 ; Beat Fierz 2 ; Robert Best 3 ; Benjamin Schuler 1 ; 1 University of Zurich, Biochemistry, Zurich, Zurich, Switzerland 2 EPFL, , Lausanne, Genf, Switzerland 3 National institutes of health, Laboratory of chemical physics, Bethesda, Maryland, United States Chromatin-binding proteins are particularly enriched in disordered and positively charged regions which facilitate electrostatic interactions with their counterparts, the highly negatively charged nucleic acids. Remarkably, such electrostatically dominated interactions can be very strong even if no well-defined structure is formed upon binding. Although such polyelectrolyte interactions have long been known in the field of soft matter physics, their importance in biology has only recently started to be recognized. A particularly interesting case are the ‘linker histones’, which bind to nucleosomes and contribute to chromatin condensation largely through the action of their long disordered and positively charged C-terminal region. Here we show, using single-molecule fluorescence spectroscopy, that the presence of disorder can convey regulatory mechanisms that would be difficult to achieve in the classical lock-and-key framework of biomolecular binding. The highly unstructured negatively charged protein prothymosin alpha, a known histone chaperone, can extract the linker histone from the nucleosome by forming a transient ternary complex. By combining the experimental results with simulations, we establish a molecular model that implies how the disordered chaperone can invade the linker histone-nucleosome complex and drive dissociation through interactions between highly charged unstructured regions.


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