A proton-gated channel identified in the centipede antenna

  • EMBO Rep. 2025 Oct 20. doi: 10.1038/s44319-025-00606-2.
Wenqi Dong  #  1  2  3 ,  Licheng Yuan  #  1  2  3 ,  Jiangming Shang  #  4  5 ,  Fan Yang  4  5 ,  Shilong Yang  1  2  3 ,  Xiancui Lu  1  2  3 ,  Qian Wang  1  2  3 ,  Anna Luo  1  2  3 ,  Jiheng Geng  1  2  3 ,  Jiatong Cheng  1  2  3 ,  Runze Li  1 ,  Yunfei Wang  6  7  8
Affiliations
  • 1. College of Wildlife and Protected Area, Northeast Forestry University, Harbin, Heilongjiang, China.
  • 2. Key Laboratory of National Forestry and Grassland Administration on Wildlife Protection, Harbin, Heilongjiang, China.
  • 3. Heilongjiang Key Laboratory of Complex Traits and Protein Machines in Organisms, Harbin, Heilongjiang, China.
  • 4. Department of Biophysics and Disease Center of the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
  • 5. Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, Zhejiang, China.
  • 6. College of Wildlife and Protected Area, Northeast Forestry University, Harbin, Heilongjiang, China. [email protected].
  • 7. Key Laboratory of National Forestry and Grassland Administration on Wildlife Protection, Harbin, Heilongjiang, China. [email protected].
  • 8. Heilongjiang Key Laboratory of Complex Traits and Protein Machines in Organisms, Harbin, Heilongjiang, China. [email protected].
  • # Contributed equally.
PMID: 41116071 DOI: 10.1038/s44319-025-00606-2
Abstract

Acid sensing is essential for various biological processes in Animals, yet it exhibits species-specific characteristics. In this study, we identified a proton-dissociation-permeated Sodium Channel (PDPNaC1) in the antennal sensory neurons of the centipede Scolopendra subspinipes mutilans. PDPNaC1, which is permeable to monovalent cations, assembles as a homotrimer. Unlike most proton-gated channels, where proton binding induces currents, PDPNaC1's transient ion-permeable state is triggered by proton dissociation. By resolving the high-resolution cryo-electron microscopy (cryo-EM) structure of PDPNaC1, combined with mutagenesis and electrophysiological analyses, we identified Gly378, rather than the Gly-Ala-Ser tract, as a key determinant of ion selectivity. Furthermore, Ser376, located in the ion-permeable pathway, likely serves as a proton-binding site, leading to an H+-blocking effect that results in proton-dissociated currents. Thus, the identification of PDPNaC1 suggests the remarkable diversity of proton responses and molecular mechanisms in DEG/ENaC family.

Keywords
Acid-sensing; Antennal Sensory Neurons; Cryo-electron Microscopy; PDPNaC1; Proton-gated Channel.
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