Protein Free Energy Landscapes Remodeled by Ligand Binding

Abstract

Glucose/galactose binding protein (GGBP) functions in two different larger systems of proteins used by enteric bacteria for molecular recognition and signaling. Here we report on the thermodynamics of conformational equilibrium distributions of GGBP. Three fluorescence components appear at zero glucose concentration and systematically transition to three components at high glucose concentration. Fluorescence anisotropy correlations, fluorescent lifetimes, thermodynamics, computational structure minimization, and literature work were used to assign the three components as open, closed, and twisted conformations of the protein. The existence of three states at all glucose concentrations indicates that the protein continuously fluctuates about its conformational state space via thermally driven state transitions; glucose biases the populations by reorganizing the free energy profile. These results and their implications are discussed in terms of the two types of specific and nonspecific interactions GGBP has with cytoplasmic membrane proteins.

Coevolutionary signals across protein lineages help capture multiple protein conformations

“…seems to be functionally relevant because it has been hypothesized to facilitate ribose transfer in the permease complex-a partially closed conformation with a more weakly bound ribose might help in providing an easier release of ribose into the membrane-bound permease (3). A similar twisted intermediate state was suggested for the D-Glucose binding protein, another member of the same family, based on experimental studies using disulfite-trapping and fluorescence spectroscopy (36,37). Very recently, accelerated molecular dynamics were used to suggest the existence of a semiclosed state for the Maltose binding protein, a member of a closely related family (38,39).…”

Variable Region Identical Immunoglobulins Differing in Isotype Express Different Paratopes

“…In enzyme kinetics, factor and/or ligand binding and differences in environmental conditions, such as temperature, pH, or ionic strength, affect enzyme function by altering the energy landscape, biasing the conformational coordinate to distinct conformational states and thus affecting the reaction coordinate and causing changes in turnover rates (45). An increasing number of studies have shown the effects of conformational sampling on ligand binding, catalysis, or product formation (46 -49).…”

An integrated perspective on RNA aptamer ligand-recognition models: clearing muddy waters

“…The recent energy landscape picture of protein folding, [16][17][18][19] in which protein dynamics are depicted as diffusion on a high-dimensional potential energy surface, established the idea that proteins can visit a pre-existing ensemble of conformations, including the 'native' structure, even in the absence of the ligand. Conformational selection proposes that the ligand selects and stabilizes a high-affinity state out of this preexisting ensemble.…”

“…Phosphotriesterase, 31 thrombin, 32 and glucose/galactose binding protein (GGBP) 19 all have two or three identifiable structures in equilibrium. Their ligand-binding mechanism has been described as CS because the ligands shift the majority of the population into the native state.…”