A Designer Peptide Toxin Isolated by Phage Display that Inhibits the Human Voltage-Gated Proton Channel, hHv1

Abstract

compartment, so that the plug and pore ring could again seal the channel. Here we prevented the intermediate from either backsliding or exiting through the lateral gate by (i) stalling a highly charged helix, the voltage sensor domain S4 of the potassium channel KvAP in the SecYEG pore and (ii) locking it between the ribosome on one side of the membrane and calmodulin on the other side. Dc was unable to gate this complex. We observed several conductivity levels, suggesting that the S4 helix was free to sample between the aqueous environment of the pore and the lipid interior. This observation (i) confirms the general view of how the translocon distinguishes membrane proteins from secretory proteins and (ii) disproves the hypothesis that the pore ring acts to maintain the membrane barrier in an active translocon. The work was supported by a grant from the Austrian science fund to Peter Pohl (P28213). 1. Saparov SM, et al. (2007) Determining the conductance of the SecY protein translocation channel for small molecules. Mol Cell 26(4):501-509. 2. Park E & Rapoport TA (2011) Preserving the membrane barrier for small molecules during bacterial protein translocation.