9OQL

Putative ATP-bound class from combined 10, 20, 30 mM ATP datasets

Summary for 9OQL

• Entry DOI: 10.2210/pdb9oql/pdb
• EMDB information: 70765
• Descriptor: Pannexin-1, PHOSPHATIDYLETHANOLAMINE, CHOLESTEROL, ... (5 entities in total)
• Functional Keywords: pannexin 1, atp release, large-pore ion channel, membrane protein, transport protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 7
• Total formula weight: 349264.11

Authors

Ruan, Z.,Li, Y.,Du, J.,Lu, W. (deposition date: 2025-05-21, release date: 2025-12-24)

Primary citation

Li, Y.,Ruan, Z.,Lee, J.,Orozco, I.J.,Zhou, E.,Du, J.,Lu, W.
Structural basis of PANX1 permeation and positive modulation by mefloquine.
Nat Commun, 16:11057-11057, 2025

PubMed Abstract: Purinergic signaling relies on ATP release through exocytosis and large-pore channels. Large-pore channels permeate both small anions like chloride and large signaling molecules like ATP, but how this broad cargo selectivity is structurally controlled remains elusive. Here we investigate PANX1, a prototypical large-pore channel, and uncover structural plasticity at the extracellular entrance formed by seven tryptophan (W74) residues. The W74 sidechains are flexible, sampling conformations that range from a constricted state permissive only to chloride to a dilated state compatible with ATP. These states are coupled to variable cation-π interactions between W74 and arginine 75 (R75), suggesting a mechanism for dynamic tuning of pore architecture and selective cargo permeation. We also identify mefloquine as a positive modulator of PANX1 that binds near the side tunnel to control ion flow through this pathway. Together, these findings define the structural principles underlying PANX1 permeation and modulation.

PubMed: 41381453
DOI: 10.1038/s41467-025-66028-9

Experimental method

ELECTRON MICROSCOPY (2.77 Å)