Referenced in: none

Automatically associated channels: HCN2

Title: A secondary structural transition in the C-helix promotes gating of cyclic nucleotide-regulated ion channels.

Authors: Michael C Puljung, William N Zagotta

Journal, date & volume: J. Biol. Chem., 2013 May 3 , 288, 12944-56

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23525108

Abstract
Cyclic nucleotide-regulated ion channels bind second messengers like cAMP to a C-terminal domain, consisting of a β-roll, followed by two α-helices (B- and C-helices). We monitored the cAMP-dependent changes in the structure of the C-helix of a C-terminal fragment of HCN2 channels using transition metal ion FRET between fluorophores on the C-helix and metal ions bound between histidine pairs on the same helix. cAMP induced a change in the dimensions of the C-helix and an increase in the metal binding affinity of the histidine pair. cAMP also caused an increase in the distance between a fluorophore on the C-helix and metal ions bound to the B-helix. Stabilizing the C-helix of intact CNGA1 channels by metal binding to a pair of histidines promoted channel opening. These data suggest that ordering of the C-helix is part of the gating conformational change in cyclic nucleotide-regulated channels.