Temperature Modulation of the DBDp53 Structure as Monitored by Static and Time-Resolved Fluorescence Combined with Molecular Dynamics Simulations
Author(s)
Date Issued
2021
Type
article
Volume
125
Issue
36
Start Page
10166
End Page
10173
Abstract
Trp146 of the p53 DNA-binding domain (DBD) was
investigated by static and time-resolved fluorescence combined with
molecular dynamics (MD) simulations at different temperatures (25,
30, 37, and 45 °C). Static emission spectra exhibit an intensity
maximum at 30 °C without any substantial peak shift, while the timeresolved
fluorescence displays a peculiar stretched exponential decay,
indicative of a structural disorder, at all of the investigated
temperatures. The stretched exponential parameter was found to
increase at 37 °C. An analysis of the MD simulation trajectories
evidenced the occurrence of jumps in the temporal evolution of the
distances between Trp146 and residues Arg110, Asp228, Cys229, and
Gln144, which are mainly responsible for Trp146 fluorescence
quenching. The times that these quenchers spend close to or far
from Trp146 can provide an explanation for the static fluorescence behavior. Further essential dynamics analysis of the MD
trajectories indicates a significant restriction of protein global motions above 37 °C. These results are consistent with a decrease in
the structural heterogeneity of DBD as the temperature increases. The results are also discussed in view of understanding how
temperature can modulate the p53 capability to binding partners, including DNA.