9oqn
Constricted-pore class from combined 0, 10, 20, 30 mM ATP datasets
Structural highlights
FunctionPANX1_HUMAN Structural component of the gap junctions and the hemichannels. May play a role as a Ca(2+)-leak channel to regulate ER Ca(2+) homeostasis.[1] [2] Publication Abstract from PubMedPurinergic 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-pi 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. Structural basis of PANX1 permeation and positive modulation by mefloquine.,Li Y, Ruan Z, Lee J, Orozco IJ, Zhou E, Du J, Lu W Nat Commun. 2025 Dec 11;16(1):11057. doi: 10.1038/s41467-025-66028-9. PMID:41381453[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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