Conformational rearrangements in the transmembrane domain of CNGA1 channels revealed by single-molecule force spectroscopy.

ABSTRACT: Cyclic nucleotide-gated (CNG) channels are activated by binding of cyclic nucleotides. Although structural studies have identified the channel pore and selectivity filter, conformation changes associated with gating remain poorly understood. Here we combine single-molecule force spectroscopy (SMFS) with mutagenesis, bioinformatics and electrophysiology to study conformational changes associated with gating. By expressing functional channels with SMFS fingerprints in Xenopus laevis oocytes, we were able to investigate gating of CNGA1 in a physiological-like membrane. Force spectra determined that the S4 transmembrane domain is mechanically coupled to S5 in the closed state, but S3 in the open state. We also show there are multiple pathways for the unfolding of the transmembrane domains, pro

SUBMITTER: Maity S 

PROVIDER: S-EPMC4432583 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature