1.D.251. The Redox-regulated Cyclodextrin-based Synthetic Channel (RCSC) Family
Natural redox-regulated channel proteins often utilize disulfide bonds as redox sensors for adaptive regulation of channel conformations in response to diverse physiological environments. Shi et al. 2024 developed novel synthetic ion channels capable of reversibly switching their ion-transport capabilities by incorporating multiple disulfide bonds into artificial systems. X-ray structural analysis and electrophysiological experiments demonstrated that these disulfide-bridged molecules possess well-defined tubular cavities and can be efficiently inserted into lipid bilayers to form artificial ion channels. The disulfide bonds in these molecules serve as redox-tunable switches to regulate the formation and disruption of ion-permeation pathways, thereby achieving a transition in the transmembrane transport process between the ON and OFF states. TRPC5 channels (TC# 1..A.4.1.7) provide examples of cystine (disulfide bond)-regulated channel proteins (see also references in TCDB authored by P. Talukdar.)
Cyclodextrins can be modified with varying numbers of thiol groups, which leads to the formation of disulfide-bridged cyclodextrin dimers.13 Shi et al. 2024 hypothesized that if the formation and disruption of ion-permeation pathways in artificial channels could be regulated by pre-introduced redox-tunable moieties, a new class of redox-regulated ion channels could be developed. This is what was achieved.