title: Molecular dynamics study on folding and allostery in RfaH.
abstract: Upon being released from the N-terminal domain (NTD), the C-terminal domain (CTD) switches from α-helix conformation to β-barrel conformation, which converts RfaH from a transcription factor into an activator of translation. The α→β conformational change may be viewed as allosteric transition. We use molecular dynamics simulations of coarse-grained off-lattice model to study the thermal folding of NTD, CTD, RfaH and the allosteric transition in CTD. The melting temperatures from the specific heat profiles indicate that the β-barrel conformation is much more stable than the α-helix conformation. Two helices in α-helix conformation have similar thermodynamic stabilities and the melting temperatures for β sheets show slight dispersion. Under the interaction with NTD, CTD is greatly stabilized and the cooperativity for thermal folding is also significantly improved. The α→β allosteric transition can be approximately described by a two-state model and three parallel pathways are identified. The transition state ensemble, quantified by a Tanford β-like parameter, resembles the α-helix and β-barrel conformations almost to the same extent.
authors.affiliation: Department of Physics, Beijing Normal University, Beijing, 100875, China.
authors.forename: Liqin
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Physics, Beijing Normal University, Beijing, 100875, China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000465:Algorithms; D000494:Allosteric Regulation; D001665:Binding Sites; D029968:Escherichia coli Proteins / Q000737:chemistry*; D007700:Kinetics; D056004:Molecular Dynamics Simulation; D010445:Peptide Elongation Factors / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D017510:Protein Folding; D055550:Protein Stability; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013696:Temperature; D013816:Thermodynamics; D015534:Trans-Activators / Q000737:chemistry*
chemical_list: D029968:Escherichia coli Proteins; D010445:Peptide Elongation Factors; C106401:RfaH protein, E coli; D015534:Trans-Activators
keywords: SOP-sidechain model; allostery; melting temperature; thermal folding; transition state ensemble