9OQQ

Human pannexin 1 channel W74A mutant with 10mM ATP

Summary for 9OQQ

• Entry DOI: 10.2210/pdb9oqq/pdb
• EMDB information: 70770
• Descriptor: Pannexin-1,RNA-directed RNA polymerase L chimera, 2-acetamido-2-deoxy-beta-D-glucopyranose (2 entities in total)
• Functional Keywords: panx1, pannexin, large pore channel, transport protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 7
• Total formula weight: 546753.30

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 (3.25 Å)