Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Concentration Dependent Ion Selectivity in VDAC: A Molecular Dynamics Simulation Study

The voltage-dependent anion channel (VDAC) forms the major pore in the outer mitochondrial membrane. Its high conducting open state features a moderate anion selectivity. There is some evidence indicating that the electrophysiological properties of VDAC vary with the salt concentration. Using a theoretical approach the molecular basis for this concentration dependence was investigated. Molecular dynamics simulations and continuum electrostatic calculations performed on the mouse VDAC1 isoform clearly demonstrate that the distribution of fixed charges in the channel creates an electric field, which determines the anion preference of VDAC at low salt concentration. Increasing the salt concentration in the bulk results in a higher concentration of ions in the VDAC wide pore. This event induces a large electrostatic screening of the charged residues promoting a less anion selective channel. Residues that are responsible for the electrostatic pattern of the channel were identified using the molecular dynamics trajectories. Some of these residues are found to be conserved suggesting that ion permeation between different VDAC species occurs through a common mechanism. This inference is buttressed by electrophysiological experiments performed on bean VDAC32 protein akin to mouse VDAC

Mechanistic studies of the biogenesis and folding of outer membrane proteins in vitro and in vivo: what have we learned to date?

Research into the mechanisms by which proteins fold into their native structures has been on-going since the work of Anfinsen in the 1960s. Since that time, the folding mechanisms of small, water-soluble proteins have been well characterised. By contrast, progress in understanding the biogenesis and folding mechanisms of integral membrane proteins has lagged significantly because of the need to create a membrane mimetic environment for folding studies in vitro and the difficulties in finding suitable conditions in which reversible folding can be achieved. Improved knowledge of the factors that promote membrane protein folding and disfavour aggregation now allows studies of folding into lipid bilayers in vitro to be performed. Consequently, mechanistic details and structural information about membrane protein folding are now emerging at an ever increasing pace. Using the panoply of methods developed for studies of the folding of water-soluble proteins. This review summarises current knowledge of the mechanisms of outer membrane protein biogenesis and folding into lipid bilayers in vivo and in vitro and discusses the experimental techniques utilised to gain this information. The emerging knowledge is beginning to allow comparisons to be made between the folding of membrane proteins with current understanding of the mechanisms of folding of water-soluble proteins

Synthesis, structural and spectral characterization of a novel NLO crystal N,N′-diphenylguanidinium picrate: diacetone solvate

An organic NLO active material N,N′-diphenylguanidinium picrate: diacetone solvate (C13H14N3+. C6H2N3O7−. 2C3H6O) (DPGPD) was synthesized and single crystals were grown by slow evaporation-solution growth technique at room temperature. DPGPD crystallizes in monoclinic crystal system with noncentrosymmetric space group, Cc confirmed by single crystal X-ray diffraction analysis. The presence of various functional groups was identified from FT-IR spectral analysis and the proton transfer during the formation of compound was confirmed by NMR spectroscopic techniques. The thermal stability was investigated by TG/DTA analyses. Optical transmittance was measured by UV–Vis–NIR spectroscopy and band gap energy was calculated. Photoluminescence spectrum was used to explore its applicability towards laser diodes. Dielectric property of the material was ascertained at different temperatures and it is found that the grown crystal has higher dielectric constant in low frequencies. Photoconductivity study revealed that DPGPD exhibits positive photoconductivity. SHG property was found to be 0.6 times higher than that of KDP

Synthesis, structural and spectral characterization of a novel NLO crystal N,N′-diphenylguanidinium picrate: diacetone solvate

An organic NLO active material N,N′-diphenylguanidinium picrate: diacetone solvate (C13H14N3+. C6H2N3O7−. 2C3H6O) (DPGPD) was synthesized and single crystals were grown by slow evaporation-solution growth technique at room temperature. DPGPD crystallizes in monoclinic crystal system with noncentrosymmetric space group, Cc confirmed by single crystal X-ray diffraction analysis. The presence of various functional groups was identified from FT-IR spectral analysis and the proton transfer during the formation of compound was confirmed by NMR spectroscopic techniques. The thermal stability was investigated by TG/DTA analyses. Optical transmittance was measured by UV–Vis–NIR spectroscopy and band gap energy was calculated. Photoluminescence spectrum was used to explore its applicability towards laser diodes. Dielectric property of the material was ascertained at different temperatures and it is found that the grown crystal has higher dielectric constant in low frequencies. Photoconductivity study revealed that DPGPD exhibits positive photoconductivity. SHG property was found to be 0.6 times higher than that of KDP