Skip to content
DraconiticResearch
Search Sources API
203,234 studies31 sourcesUpdated 22 min ago
Peer-reviewedCC BYBioinformatics advances

Decoding channel pore dynamics mechanism in Anopheles gambiae Orco homotetramer.

  • Vaanathi Chidambara Thanu1
  • Amara Jabeen1
  • Georgia Kythreoti2,3
  • Kostas Iatrou3
  • Spyros E Zographos4
  • Philip W Taylor1
  • Shoba Ranganathan1
4 affiliations
  1. 1Applied BioSciences, Macquarie University, Sydney, NSW 2109, Australia.
  2. 2Department of Natural Sciences - Deree, The American College, Athens 15342, Greece.
  3. 3Institute of Biosciences & Applications, National Centre for Scientific Research "Demokritos", Athens 15341, Greece.
  4. 4Institute of Chemical Biology, National Hellenic Research Foundation, Athens 11635, Greece.
Read full textPDFDOICite

Abstract

Motivation

Insect odorant receptors (iORs) essential for olfaction function as 7-transmembrane-domain (7TM) ion channels. iORs form tetrameric complexes that include a highly conserved odorant receptor co-receptor (Orco). Functional Orco homotetramers have also known to form ex vivo. Blocking Orco ex vivo and in vivo disrupts olfactory signalling, making it a promising target for functional intervention. Understanding its gating behaviour is critical for developing strategies to disrupt odour-guided behaviours in disease-vector insects. Thus, insights into the dynamic gating of the Anopheles gambiae Orco have implications on the rational design of vector-control strategies against malaria. We studied molecular dynamics (MD) simulations on homotetrameric AgamOrco models generated using template-based modelling (TBM) and AlphaFold3 (AF3), to investigate ligand-dependent pore dynamics. Agonist and antagonist bound systems were analysed to understand the ligand-dependent gating.Results

Our results show that apo and antagonistic IPC-bound AgamOrco homotetramer models remain in a stable, closed, and non-conductive state across both models. TBM, but not AF3, successfully captures agonistic VUAA1-induced activation, consistent with experimental observations, exhibiting asymmetric pore widening and conformational changes. Antagonist displacement simulations confirm IPC-mediated pore closure. Overall, the TBM AgamOrco model provides a reliable framework for structure-guided discovery of novel agents for control of insect pests and vector diseases.

Related

  1. The MscS channel from Corynebacterium glutamicum uses a non-canonical gating mechanism
    Y. Nakayama, G. Hiotis, T. Walz
    bioRxivPreprintCC BYFull textBiophysicsbioRxiv
  2. A Binding Site for CVN293 Reveals a Mechanism for Allosteric Control of THIK-1 K2P Channel Gating
    M. Devlin, K. Rodstrom, C. Benkerdagh +11
    bioRxivPreprintCC BYFull textBiophysicsbioRxiv
  3. A conserved conformation-dependent mechanism for the TREK two-pore domain potassium channel inhibitors carvedilol and fluphenazine
    Joelle Reich, Paul M. Riegelhaupt, Stephen J. Tucker +1
    Molecular PharmacologyPeer-reviewedCC BY 4.0Full textMolecular biology & gene regulationPMC
  4. A histidine-mediated supramolecular mechanism links temperature and pH activation of the sperm channel CatSper
    Billy Zhao, Shweta Bhagwat, Juan Ferreira +6
    PLOS BiologyPeer-reviewedCC BYFull textBiophysicsPhysiologyPLOSEurope PMC
  5. Microbiome, anti-infectives, and artificial intelligence: Decoding host-microbe dynamics.
    Xiang Li, Shimiao Shao, Yueyue He +1
    Infectious diseases & immunityPeer-reviewedCC BY-NC-NDFull textMolecular biology & gene regulationEurope PMC

Cite

BibTeXRIS
BibTeX
@article{thanu2026decoding,
  title = {{Decoding channel pore dynamics mechanism in Anopheles gambiae Orco homotetramer.}},
  author = {Vaanathi Chidambara Thanu and Amara Jabeen and Georgia Kythreoti and Kostas Iatrou and Spyros E Zographos and Philip W Taylor and Shoba Ranganathan},
  journal = {Bioinformatics advances},
  year = {2026},
  month = oct,
  doi = {10.1093/bioadv/vbag295},
  url = {https://europepmc.org/article/MED/42899295},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Decoding channel pore dynamics mechanism in Anopheles gambiae Orco homotetramer.
AU  - Vaanathi Chidambara Thanu
AU  - Amara Jabeen
AU  - Georgia Kythreoti
AU  - Kostas Iatrou
AU  - Spyros E Zographos
AU  - Philip W Taylor
AU  - Shoba Ranganathan
PY  - 2026
DA  - 2026/10/06
JO  - Bioinformatics advances
DO  - 10.1093/bioadv/vbag295
UR  - https://europepmc.org/article/MED/42899295
AB  - Motivation  Insect odorant receptors (iORs) essential for olfaction function as 7-transmembrane-domain (7TM) ion channels. iORs form tetrameric complexes that include a highly conserved odorant receptor co-receptor (Orco). Functional Orco homotetramers have also known to form ex vivo. Blocking Orco ex vivo and in vivo disrupts olfactory signalling, making it a promising target for functional intervention. Understanding its gating behaviour is critical for developing strategies to disrupt odour-guided behaviours in disease-vector insects. Thus, insights into the dynamic gating of the Anopheles gambiae Orco have implications on the rational design of vector-control strategies against malaria. We studied molecular dynamics (MD) simulations on homotetrameric AgamOrco models generated using template-based modelling (TBM) and AlphaFold3 (AF3), to investigate ligand-dependent pore dynamics. Agonist and antagonist bound systems were analysed to understand the ligand-dependent gating.Results  Our results show that apo and antagonistic IPC-bound AgamOrco homotetramer models remain in a stable, closed, and non-conductive state across both models. TBM, but not AF3, successfully captures agonistic VUAA1-induced activation, consistent with experimental observations, exhibiting asymmetric pore widening and conformational changes. Antagonist displacement simulations confirm IPC-mediated pore closure. Overall, the TBM AgamOrco model provides a reliable framework for structure-guided discovery of novel agents for control of insect pests and vector diseases.
SN  - 2635-0041
ER  -