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oai:figshare.com:article/34049527 2026-10-01T17:47:01Z category_4 category_12 category_13 category_14 category_15 category_16 category_64 category_128 portal_5 item_type_1 month_year_10_2026

<p><i>egl-2</i> encodes the sole <i>C. elegans</i> EAG potassium channel.</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 molecular mechanism important sleep regulator findings identify egl div >< p caenorhabditis elegans </ similarly suppresses sleep 2 functions cell elegans </ suppresses sleep kcnh voltage vivo </ central sleep conserved cnbhd shifts voltage second substitution negative potentials intrinsic ligand g574r ), function effects corresponding residue <p>(<b>A</b>) Schematic of the domain organization and topology of the <i>C. elegans</i> EGL-2/EAG potassium channel. EGL-2 contains six transmembrane segments (S1-S6) and several intracellular domains, including an N-terminal PAS domain (orange) and a cyclic nucleotide-binding homology domain (CNBHD, cyan) with an intrinsic ligand (magenta). S1-S4 form a voltage sensor domain (green), whereas S5-S6 form a pore domain (yellow). The red star indicates the glycine residue (G574) mutated in <i>egl-2(sy985)</i> and <i>egl-2(tan200)</i>. Grey lines indicate the N-terminal region, interdomain linkers, and the C-terminus. The light gray rectangle indicates the plasma membrane. (<b>B</b>) Amino acid sequence alignment of a conserved region within the CNBHD of EAG1 orthologs from the indicated species. The glycine residue corresponding to G574 in EGL-2 (highlighted in yellow) is highly conserved and resides within the first α-helix of the CNBHD. Asterisks indicate identical residues; colons indicate conserved residues. (<b>C-F</b>) Structural models of EGL-2/EAG predicted by AlphaFold3, shown in cartoon representations, with the residue G574 highlighted in red. (C) Side view of a single subunit; (D) Side view of the tetrameric EGL-2 channel; (E) Bottom view of the tetrameric channel showing only the PAS domains and CNBHDs for better visualization of the location of the residue G574; (F) Magnified view of the region between two adjacent CNBHDs, as boxed in (E). Domains are colored as indicated in the diagram at the bottom, with residue numbering based on EGL-2 isoform a. The red star indicates the glycine (G574) mutated in <i>egl-2(sy985)</i> and <i>egl-2(tan200)</i>. (<b>G-H</b>) Sphere representations of the AlphaFold3-predicted structure of the homotetrameric EGL-2 channel, showing the inter-subunit arrangement of the PAS domains and CNBHDs within the intracellular ring. The four subunits are colored yellow, green, orange, and purple. Other domains are omitted for better visualization of G574 (in red) at the CNBHD-CNBHD interface<b>. (G)</b> Bottom view of the intracellular gating ring of EGL-2 channel. The CNBHDs form the inner ring, with the PAS domains positioned peripherally. <b>(H)</b> Side view of two CNBHDs from adjacent subunits, highlighting the position of G574 (in red) at the interface, generated by a 90° downward rotation of the bottom views shown in (G) and displayed at higher magnification, with the PAS domains omitted for clarity. Top, opaque sphere representation of two adjacent CNBHDs; bottom, magnified view of a smaller region containing the CNBHD-CNBHD interface at 70% transparency.</p> 2026-10-01T17:46:48Z Image Figure 10.1371/journal.pgen.1012255.g002 https://figshare.com/articles/figure/_p_i_egl-2_i_encodes_the_sole_i_C_elegans_i_EAG_potassium_channel_p_/34049527 CC BY 4.0