2026-10-14T14:55:36Z
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2026-10-01T17:46:52Z
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<p>Conserved CNBHD-CNBHD interface in EAG and ERG channels.</p>
Xinyu Huang (679541)
Sudharsan Kannan (25158064)
Gail A. Robertson (15007385)
Han Wang (254423)
Biochemistry
Cell Biology
Genetics
Molecular Biology
Neuroscience
Physiology
Cancer
Hematology
regulate neuronal excitability
promoting neuron ala
influence channel gating
hallmark cyclic nucleotide
genetic analysis demonstrated
forward genetics reveals
electrophysiological analysis showed
dependent channel activation
calcium imaging showed
binding homology domains
adjacent channel subunits
accelerates activation kinetics
subfamily kcnh channels
conserved gating mechanism
important sleep regulator
findings identify egl
div >< p
caenorhabditis elegans </
similarly suppresses sleep
2 functions cell
elegans </
suppresses sleep
kcnh voltage
vivo </
conserved cnbhd
central sleep
shifts voltage
second substitution
negative potentials
intrinsic ligand
g574r ),
function effects
corresponding residue
<p>Sphere representations of the intracellular gating ring of the following three homotetrameric channels: <i>C. elegans</i> EGL-2 (AlphaFold3-predicted structure), rEag1 (cryo-EM structure; PDB: 5K7L), and hERG (cryo-EM structure; PDB: 5VA1). The PAS domains and CNBHDs from each of the four subunits are colored yellow, green, orange, and purple; other domains are omitted for clarity. The EGL-2 G574 residue and the corresponding residues rEag1 G561 and hERG G749, highlighted in red, are all located at the conserved CNBHD-CNBHD interface. (<b>A</b><b>, C, E</b>) Bottom views of the intersubunit structural arrangement of the PAS domain and CNBHD within the intracellular gating ring of (A) EGL-2, (C) rEag1, and (E) hERG. The CNBHDs form an inner ring, with PAS domains positioned peripherally. (<b>B</b><b>, D, F</b>) Side views of two CNBHDs from adjacent subunits of (B) EGL-2, (D) rEag1, and (F) hERG, generated by a 90° downward rotation of the bottom views shown in (A, C, E) and displayed at higher magnification, with the PAS domains omitted for clarity. Top, opaque sphere representation of two adjacent CNBHDs; bottom, a magnified view of a smaller region containing the CNBHD-CNBHD interface at 70% transparency, for better visualization of the conserved glycine residue (in red) at the interface.</p> <p>(TIF)</p>
2026-10-01T17:54:06Z
Image
Figure
10.1371/journal.pgen.1012255.s002
https://figshare.com/articles/figure/_p_Conserved_CNBHD-CNBHD_interface_in_EAG_and_ERG_channels_p_/34049491
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