- TRP and TRPL in photoreceptors of P. americana
Insect photoreceptors utilize two light-activated channels, TRP and TRPL, in their phototransduction cascades, but the American cockroach Periplaneta americana depends strongly on TRPL. Saari et al. show that TRPL generates high-gain and high-noise phototransduction suitable for dim light vision.
- Protein ligands for studying ion channel proteins
Chavan et al. highlight work showing that a monobody can inhibit a fluoride channel using a mechanism similar to that of a scorpion toxin blocker of potassium channels.
- Sodium channel block
A number of different drugs block sodium channels, but their mechanism of block is unclear. Tikhonov and Zhorov combine homology modeling with ligand docking and propose a pharmacophore for sodium channel blockers involving cationic and aromatic moieties.
- Monobody block of dual topology fluoride channels
Fibronectin domain monobodies bind to both sides of Fluc Fl− channels in a negatively cooperative way, but crystal structures show two monobodies binding simultaneously. Turman and Stockbridge resolve this contradiction by showing that monobodies block channel pores by means of a negatively charged loop.
- Substrate-induced trapping of a transporter
A conserved glutamic acid residue is thought to occupy three different conformations in the transport pathway of CLC H+/Cl− exchangers. Vien et al. provide functional evidence that the most central of these three positions is adopted by CLC-ec1 during transport and is stabilized by hydrogen bonds.
- Electrostatic tuning of CFTR’s open states
Gating of the CFTR channel is coupled to ATP hydrolysis such that two open states can be identified under certain conditions. Zhang and Hwang find that pore-lining mutations differentially affect the permeation properties of these open states and suggest that the internal vestibule expands upon ATP hydrolysis.
- VSD regulation of NaV inactivation
Hsu et al. probe voltage-gated Na+ channels that are inactivation deficient with voltage-clamp fluorometry. They find that in the time domain of an action potential, the voltage-sensing domain (VSD) of domain IV regulates fast inactivation onset while the domain III VSD determines its recovery.