Voltage sensor domains (VSD) of voltage-dependent ion channels share a basic molecular structure with a voltage-sensing phosphatase and a voltage-gated proton channel. The VSD senses and responds to changes in the membrane potential by undergoing conformational changes associated with the movement of the charged arginines located on the S4 segment. Although several functional and structural studies have provided useful information about the conformational changes in many ion channels, a detailed and unambiguous explanation has not been published. Therefore, understanding the principle of voltage-dependent gating at an atomic level is required. In this study, we took advantage of the available spin labeling electron paramagnetic resonance spectrometry data and computational methods to investigate the structure and dynamic properties of the Up-state (activated) and Down-state (resting) conformations of the VSD by means of all-atom molecular dynamics (MD) simulations. The MD results of the Down conformation determined in bilayers with and without lipid phosphates both revealed a different shape of the aqueous crevice, in which more water molecules surround and fill the intracellular crevice in its Down state than in its Up state. The solvent accessible surface within the crevice has a complementary shape that can account for water-mediated interactions between the voltage sensor and the lipid bilayer. The results support the previously reported experimental data.
investigate a wide protein concentration and pH range of 2 mg/mL % [Protein] % 500 mg/mL and 3.0 % pH % 11 and find clear evidence for pH and concentration dependencies of conformation from our SANS data. The data are successfully modeled using the random-phase approximation (RPA), where we use a phenomenological model for the form factor that is able to capture contributions from both monomers and clusters in solution. Owing to the separability of the form factor into contributions from monomers and clusters, we are able to obtain structure factors that reflect monomer-monomer, monomer-cluster, and cluster-cluster correlations in solution, which allows us to gain realistic insights into packing and intermolecular interactions at high concentrations. We use these data as inputs into a modification of the model developed by Minton for protein mixtures, which can accurately capture the contributions of monomer and clustered species to model the concentration and pH dependent viscosity of BSA and the IgG1 solution.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.