Revealing the Structural Contributions to Thermal Adaptation of the TATA-Box Binding Protein: Molecular Dynamics and QSPR Analyses

The
TATA-box binding protein (TBP) is an important element of the
transcription machinery in archaea and eukaryotic organisms. TBP is
expressed in organisms adapted to different temperatures, indicating
a robust structure, and experimental studies have shown that the mid-unfolding
temperature (Tm) of TBP is directly correlated with the optimal growth
temperature (OGT) of the organism. To understand which are the relevant
structural requirements for its stability, we present the first structural
and dynamic computational study of TBPs, combining molecular dynamics
(MD) simulations and a quantitative structure–property relationship
(QSPR) over a set of TBPs of organisms adapted to different temperatures.
We found that the main structural properties of TBP used to adapt
to high temperatures are an increase in the ease of desolvation of
charged residues at the surface, an increase in the local resiliency,
the presence of Leu clusters in the protein core, and an increase
in the loss of hydrophobic packing in the N-terminal subdomain. In
view of our results, we consider that TBP is a good model to study
thermal adaptation, and our analysis opens the possibility of performing
protein engineering on TBPs to study transcription at high or low
temperatures.