Protein ligands for studying ion channel proteins

Abstract

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.

Figure 1.

Charybdotoxin block of potassium channels. (A) Cartoon illustrating charybdotoxin binding to the outer pore of the BK channel and the position of a basic residue near to where potassium ions bind within the outer pore of the channel. The cartoon is reproduced from MacKinnon and Miller (1988). (B) X-ray structure of the Kv1.2/2.1 paddle chimera in complex with charybdotoxin (PDB accession no. 4JTA). Only S5-S6 helices are shown for clarity, with neighboring subunits colored white or wheat. The toxin is colored blue, with K27 shown in stick representation (carbon colored yellow and nitrogen blue).

Figure 2.

Model of the Bpe Fluc channel with L3 monobodies bound. Ribbon representation of a model of the Bpe Fluc channel in complex with L3 monobody, constructed using the x-ray structure of Bpe Fluc in complex with L2 monobody (PDB accession no. 5FXB). Two ion permeation pathways in the antiparallel dimer are positioned lateral to the critical Phe residues (F82 and F85; yellow stick). Each L3 monobody (blue) inserts the FG loop into the pore, with E79 shown in stick representation (carbon colored yellow and oxygen red).