High-Affinity Interactions of Beryllium(2+) with Phosphatidylserine Result in a Cross-Linking Effect Reducing Surface Recognition of the Lipid.

Beryllium has multiple industrial applications, but its manufacture is associated with a serious occupational risk of developing chronic inflammation in the lungs known as berylliosis, or chronic beryllium disease. Although the Be-induced abnormal immune responses have recently been linked to a specific MHC-II allele, the nature of long-lasting granulomas is not fully understood. Here we show that Be binds with a micromolar affinity to phosphatidylserine (PS), the major surface marker of apoptotic cells.

The cytoplasmic cage domain of the mechanosensitive channel MscS is a sensor of macromolecular crowding.

Cells actively regulate the macromolecular excluded volume of the cytoplasm to maintain the reciprocal fraction of free aqueous solution that is optimal for intracellular processes. However, the mechanisms whereby cells sense this critical parameter remain unclear. The mechanosensitive channel of small conductance (MscS channel), which is the major regulator of turgor in bacteria, mediates efflux of small osmolytes in response to increased membrane tension.

Effects on membrane lateral pressure suggest permeation mechanisms for bacterial quorum signaling molecules.

Quorum sensing is an intricate example of "social" behavior in microbial communities mediated by small secreted molecules (autoinducers). The mechanisms of membrane permeation remain elusive for many of them. Here we present the assessment of membrane permeability for three natural autoinducers and four synthetic analogues based on their polarity, surface activity, affinity for lipid monolayers, and ability to induce lateral pressure changes in the inner E.

The pathway and spatial scale for MscS inactivation.

The mechanosensitive channel of small conductance (MscS) is a bacterial tension-driven osmolyte release valve with homologues in many walled eukaryotic organisms. When stimulated by steps of tension in excised patches, Escherichia coli MscS exhibits transient opening followed by reversible adaptation and then complete inactivation. Here, we study properties of the inactivation transition, which renders MscS nonconductive and tension insensitive.

Effects of GsMTx4 on bacterial mechanosensitive channels in inside-out patches from giant spheroplasts.

GsMTx4 is a 34-residue peptide isolated from the tarantula Grammostola spatulata folded into an inhibitory cysteine knot and it selectively affects gating of some mechanosensitive channels. Here we report the effects of cytoplasmic GsMTx4 on the two bacterial channels, MscS and MscL, in giant Escherichia coli spheroplasts. In excised inside-out patches, GsMTx4 sensitized both channels to tension by increasing the opening rate and decreasing the closing rate.

Adaptive behavior of bacterial mechanosensitive channels is coupled to membrane mechanics.

Mechanosensitive channel of small conductance (MscS), a tension-driven osmolyte release valve residing in the inner membrane of Escherichia coli, exhibits a complex adaptive behavior, whereas its functional counterpart, mechanosensitive channel of large conductance (MscL), was generally considered nonadaptive. In this study, we show that both channels exhibit similar adaptation in excised patches, a process that is completely separable from inactivation prominent only in MscS. When a membrane patch is held under constant pressure, adaptation of both channels is manifested as a reversible current decline.

Gadolinium ions block mechanosensitive channels by altering the packing and lateral pressure of anionic lipids.

Effects of polyvalent ions on the lateral packing of phospholipids have been known for decades, but the physiological consequences have not been systematically studied. Gd(3+) is a relatively nonspecific agent that blocks mechano-gated channels with a variable affinity. In this study, we show that the large mechanosensitive channel MscL of Escherichia coli is effectively blocked by Gd(3+) only when reconstituted with negatively charged phospholipids (e.

The tension-transmitting 'clutch' in the mechanosensitive channel MscS.

Under prolonged stimulation, the mechanosensitive channel MscS of Escherichia coli enters a tension-insensitive inactivated state. We transformed the delipidated crystal structure and restored the link between lipid-facing TM1 and TM2 and gate-forming TM3 helices. Joining the conserved Phe68 of TM2 with Leu111 of TM1, this buried contact mediated opening in steered molecular dynamics simulations with forces applied to the peripheral helices.

The membrane lateral pressure-perturbing capacity of parabens and their effects on the mechanosensitive channel directly correlate with hydrophobicity.

Lipid bilayers provide a natural anisotropic environment for membrane proteins and can serve as apolar reservoirs for lipid-derived second messengers or lipophilic drugs. Partitioning of lipophilic agents changes the lateral pressure distribution in the bilayer, affecting integral proteins. p-Hydroxybenzoic acid esters (parabens) are amphipathic compounds widely used as food and cosmetics preservatives, but the mechanisms of their broad antibacterial action are unknown.

Mechanosensitive channel MscS in the open state: modeling of the transition, explicit simulations, and experimental measurements of conductance.

Mechanosensitive channels of small conductance (MscS) are ubiquitous turgor pressure regulators found in many walled cells and some intracellular organelles. Escherichia coli MscS acting as a tension-activated osmolyte release valve shows a nonsaturable conductance (1.2 nS in a 39 mS/cm electrolyte) and weak preference for anions.