9on6 | pdb_00009on6

The pre-open state 2 structure of human P2X2 receptor channel in lipid nanodiscs with free ATP and sodium

Structural highlights

9on6 is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.6Å
Ligands:	ATP, NAG
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

P2RX2_HUMAN Rare autosomal dominant non-syndromic sensorineural deafness type DFNA. The disease is caused by variants affecting the gene represented in this entry.

Function

P2RX2_HUMAN ATP-gated nonselective transmembrane cation channel permeable to potassium, sodium and calcium (PubMed:10570044, PubMed:31636190). Activation by extracellular ATP induces a variety of cellular responses, such as excitatory postsynaptic responses in sensory neurons, neuromuscular junctions (NMJ) formation, hearing, perception of taste and peristalsis (By similarity). In the inner ear, regulates sound transduction and auditory neurotransmission, outer hair cell electromotility, inner ear gap junctions, and K(+) recycling (PubMed:23345450). Mediates synaptic transmission between neurons and from neurons to smooth muscle (By similarity).[UniProtKB:Q8K3P1]^[1] ^[2] ^[3]

References

↑ Lynch KJ, Touma E, Niforatos W, Kage KL, Burgard EC, van Biesen T, Kowaluk EA, Jarvis MF. Molecular and functional characterization of human P2X(2) receptors. Mol Pharmacol. 1999 Dec;56(6):1171-81. PMID:10570044 doi:10.1124/mol.56.6.1171
↑ Yan D, Zhu Y, Walsh T, Xie D, Yuan H, Sirmaci A, Fujikawa T, Wong AC, Loh TL, Du L, Grati M, Vlajkovic SM, Blanton S, Ryan AF, Chen ZY, Thorne PR, Kachar B, Tekin M, Zhao HB, Housley GD, King MC, Liu XZ. Mutation of the ATP-gated P2X(2) receptor leads to progressive hearing loss and increased susceptibility to noise. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2228-33. PMID:23345450 doi:10.1073/pnas.1222285110
↑ George B, Swartz KJ, Li M. Hearing loss mutations alter the functional properties of human P2X2 receptor channels through distinct mechanisms. Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22862-22871. PMID:31636190 doi:10.1073/pnas.1912156116

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OCA

[1] Lynch KJ, Touma E, Niforatos W, Kage KL, Burgard EC, van Biesen T, Kowaluk EA, Jarvis MF. Molecular and functional characterization of human P2X(2) receptors. Mol Pharmacol. 1999 Dec;56(6):1171-81. PMID:10570044 doi:10.1124/mol.56.6.1171

[2] Yan D, Zhu Y, Walsh T, Xie D, Yuan H, Sirmaci A, Fujikawa T, Wong AC, Loh TL, Du L, Grati M, Vlajkovic SM, Blanton S, Ryan AF, Chen ZY, Thorne PR, Kachar B, Tekin M, Zhao HB, Housley GD, King MC, Liu XZ. Mutation of the ATP-gated P2X(2) receptor leads to progressive hearing loss and increased susceptibility to noise. Proc Natl Acad Sci U S A. 2013 Feb 5;110(6):2228-33. PMID:23345450 doi:10.1073/pnas.1222285110

[3] George B, Swartz KJ, Li M. Hearing loss mutations alter the functional properties of human P2X2 receptor channels through distinct mechanisms. Proc Natl Acad Sci U S A. 2019 Nov 5;116(45):22862-22871. PMID:31636190 doi:10.1073/pnas.1912156116

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9on6 | pdb_00009on6

The pre-open state 2 structure of human P2X2 receptor channel in lipid nanodiscs with free ATP and sodium

Structural highlights

Disease

Function

References

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