Book of Abstracts: Albany 2005
Geometry of the Nucleosome's Superhelix: Ideal and Actual Structures
The nucleosome is a histone DNA complex that folds 147 basepair of DNA into 1.7 turns of a left-handed superhelix. Idealized models of the superhelix often assume a minimal path around the histone core with an average bend of 360°*1.7/147 ∼ 4.2°/bp, constant Twist, and constant Rise. X-ray structures of nucleosomes indicate that actual nucleosomes have nearly two times the minimum bend required. Here we determine the interbasepair helical parameters (Roll, Tilt, Twist, Shift, Slide, Rise) for the available x-ray structures and compare them to results from a 10ns molecular dynamics simulation of a nucleosome. Fourier analysis of the helical parameters is used to identify structural variations in the superhelix on different length scales. We find that more than one wavelength, i.e., Fourier mode, is needed to reconstruct the superhelix. Required modes represent variations in the helical parameters with wavelengths of 10.4bp and 147bp. The first is the well-known variation in Roll and Tilt associated with the helix repeat. The second suggests that a nucleosome requires contact between the histone core and all 147bp. Additional modes are required to reconstruct an atomic model of the superhelix with less than a 4.5Å RMSD from the actual superhelix. These modes are "corrections" to the primary variations with wavelengths of 10.4bp and 147bp. Shift and Slide, which are often ignored in idealized models of the nucleosome, are a required component of the primary structure. Thus an actual nucleosome requires shear as well as bend.
Thomas C. Bishop
Dept. Environmental Health Sciences
Top: Far Left: Snapshot of a nucleosome taken from a 10ns molecular dynamics simulation. Left: Reconstruction of the nucleosomal superhelix using all six helical parameters. Data has been averaged over 5.5ns (light grey line in plots). Root mean square deviation (RMSD) between reconstructed superhelix and snapshot is 1.6Å. Middle: Reconstruction using smoothed helical parameter data (dark solid line in plots). Smoothing includes 6 Fourier modes. RMSD is 4.2Å. Right: An ideal nucleosomal superhelix that has constant Twist and Rise and one Fourier mode for the other helical parameters (dotted line in plots). This model captures the overall superhelical pitch and diameter, but there is an RMSD of 12.2Å between the atomic model (not shown) and the indicated snapshot. Bottom: Helical parameter data for the reconstructions. The time average data is not smooth (light grey line). Fourier smoothed data (dark solid line) that contains 6 of 72 possible Fourier modes yields a close approximation to the actual superhelix. Asymmetries in Twist and Rise and a long wavelength variation in Slide, Roll, and Rise are evident and are necessary for proper representation of the nucleosomal superhelix. An ideal superhelix with constant Twist and Rise and one Fourier mode for all other variables appears as a dotted line.