Recombinant Haplopelma schmidti Tau-theraphotoxin-Hs1a

Selectively activates the heat-activated TRPV1 channel. It binds to TRPV1 in an open state-dependent manner, trapping it there to produce irreversible currents. It binds to the outer edge of the external pore of TRPV1 in a counterclockwise configuration, using a limited protein-protein interface and inserting hydrophobic residues into the bilayer. It also partitions naturally into membranes, with the two lobes exhibiting opposing energetics for membrane partitioning and channel activation. In addition, the toxin disrupts a cluster of hydrophobic residues behind the selectivity filter that are critical for channel activation.