Thermal Adaptation Strategies used by TBP

Abstract

The TATA binding protein (TBP) is a monomeric transcription factor present in archaea and eukarya, in organisms adapted to temperatures spread over a 100°C range. Thermal adaptation implies a balance between stabilization and function, which entails keeping ligand selectivity and also the amplitude of conformational fluctuations within physiologically reasonable bounds. To explore relevant contributions to thermal adaptation of the TBP fold, we perturbed the native structures of six TBP variants coming from organisms with optimal growth temperatures between 10°C and 105°C, with molecular dynamics simulations at 273, 298, 323, 348 and 373K, and 1 atm pressure, with the CHARMM27 forcefield in NAMD, for 11 ns each. We characterized the temperature response of free energy components obtained using the MM-PBSA approach. Hyperthermophilic TBPs have a less steep response of their free energy to temperature than the mesophiles or the psycrophile, suggesting that TBP alters the curvature of its free energy surface as a global stabilization strategy; this coincides qualitatively with a measure of resiliency derived from the fluctuations of H atoms over 100 ps intervals. The van der Waals energy becomes less attractive with increasing temperature, and this correlates with a decrease in protein density and an increase in the number of sampled sidechain rotamers, but the steepness of the response is not correlated to the thermal stability of TBP. The electrostatic energy decreases upon temperature increase, and opposes all other internal energy components. This electrostatic stabilization with increasing temperature is due to the decrease in dielectric properties of water, and is reflected in an increase in the number of salt bridges at the expense of TBP-water interactions; this is particularly effective in hyperthermophiles.Funding: Macroproyecto de Tecnologias de la Informacion y la Computacion (UNAM),SEP-FOMES 2000 Computo Cientifico and Consolidacion PROMEP-UAEM 2007