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bioRxiv · 10.1101/550970

Electron cryo-microscopy structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome.

Armache, J.-P.·Gamarra, N.·Johnson, S. L.·Leonard, J. D.·Wu, S.·Narlikar, G. J.·Cheng, Y.
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Abstract

The SNF2h remodeler slides nucleosomes most efficiently as a dimer, yet how the two protomers avoid a tug-of-war is unclear. Furthermore, SNF2h couples histone octamer deformation to nucleosome sliding, but the underlying structural basis remains unknown. Here we present cryo-EM structures of SNF2h-nucleosome complexes with ADP-BeFx that capture two reaction intermediates. In one structure, histone residues near the dyad and in the H2A-H2B acidic patch, distal to the active SNF2h protomer, are disordered. The disordered acidic patch is expected to inhibit the second SNF2h promoter, while disorder near the dyad is expected to promote DNA translocation. The other structure doesnt show octamer deformation, but surprisingly shows a 2bp translocation. FRET studies indicate that ADP-BeFx predisposes SNF2h-nucleosome complexes for an elemental translocation step. We propose a model for allosteric control through the nucleosome, where one SNF2h protomer promotes asymmetric octamer deformation to inhibit the second protomer, while stimulating directional DNA translocation. One sentence summaryCryo-EM structures capture different conformational states of chromatin remodeler-nucleosome complexes.

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Armache, J.-P., Gamarra, N., Johnson, S. L., Leonard, J. D., Wu, S., Narlikar, G. J., Cheng, Y.. 2019-02-15. Electron cryo-microscopy structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome.. https://doi.org/10.1101/550970

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