A bivalent tarantula toxin activates the capsaicin receptor, TRPV1, by targeting the outer pore domain

Toxins have evolved to target regions of membrane ion channels that underlie ligand binding, gating, or ion permeation, and have thus served as invaluable tools for probing channel structure and function. Here, we describe a peptide toxin from the Earth Tiger tarantula that selectively and irreversibly activates the capsaicin- and heat-sensitive channel, TRPV1. This high-avidity interaction derives from a unique tandem repeat structure of the toxin that endows it with an antibody-like bivalency. The "double-knot" toxin traps TRPV1 in the open state by interacting with residues in the presumptive pore-forming region of the channel, highlighting the importance of conformational changes in the outer pore region of TRP channels during activatio

Grain refinement of an extruded Mg alloy via na microalloying

The effect of 0.3 wt pct Na on the microstructure of extruded alloy Mg-2Sn-1Zn is examined. We report that Na stabilizes the Mg2Sn phase, resulting in its precipitation during extrusion under conditions where a solid solution is otherwise expected. This effect appears to be thermodynamic in nature and is different from the kinetic enhancement of low- temperature aging reported by Mendis et al. [Phil. Mag. Letters, 86 (2006), 443]. The precipitates of the current study enable useful refinement of the grain size