New evidence from NMR spectroscopy suggests that histone tails remain
highly dynamic even in the condensed state of chromatin. To probe the
dynamic behavior of H4 histone N-terminal tail in greater detail, we
prepared a sample of mononucleosome containing 15N, 13 C-labeled H4
histone. The HSQC spectrum of this sample features observable signals
from the first fifteen residues in H4; half of these signals have been
successfully assigned and used for site-specific 15N relaxation
measurements. The experimentally obtained chemical shifts and relaxation
rates paint the picture of moderately mobile H4 tail with random-coil-like
conformational properties. We have also recorded a μs-long MD trajectory
of mononucleosome in the explicit TIP4P-D solvent, which has been
designed specifically for (partially) disordered protein systems. This
trajectory successfully reproduced the experimentally measured chemical
shifts and relaxation rate constants. According to the MD data, the positively
charged H4 tail hovers over the negatively charged ds-DNA, making
transient contacts with both DNA backbone and major/minor grooves. This
type of behavior, underpinned by electrostatic attraction and characterized
by substantial mobility of H4 tail relative to the DNA chain, can be
classified as "fuzzy interaction".