Agonist binding evokes extensive conformational changes in the extracellular domain of the ATP-gated human P2X1 receptor ion channel

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 12, 2012, Pages 4663-4667

  Roberts, Jonathan A ^a   Allsopp, Rebecca C ^a   El Ajouza, Sam ^a   Vial, Catherine ^a   Schmid, Ralf ^a   Young, Mark T ^b   Evans, Richard J ^a  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

^b CARDIFF UNIVERSITY   (United Kingdom)

Author keywords

Cysteine scanning; Purinergic receptor

Indexed keywords

ADENOSINE TRIPHOSPHATE; CYSTEINE; PURINERGIC P2X1 RECEPTOR;

ARTICLE; BINDING KINETICS; BIOTINYLATION; CARBOXY TERMINAL SEQUENCE; CELL MEMBRANE; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; DISULFIDE BOND; ELECTRON MICROSCOPY; INHIBITION KINETICS; NONHUMAN; PEPTIDE MAPPING; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PURIFICATION; PROTEIN STRUCTURE; PROTEIN SUBUNIT; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS;

ADENOSINE TRIPHOSPHATE; ANIMALS; BINDING SITES; BIOTINYLATION; DISULFIDES; HUMANS; IONS; MICROSCOPY, ELECTRON; MOLECULAR CONFORMATION; MUTAGENESIS; OOCYTES; PROTEIN BINDING; PROTEIN CONFORMATION; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, PURINERGIC P2X1; XENOPUS;

EID: 84858665860     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1201872109     Document Type: Article

References (22)

1. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413-492. (Pubitemid 28477681)
2. Burnstock G (2006) Historical review: ATP as a neurotransmitter. Trends Pharmacol Sci 27:166-176.
3. Surprenant A, North RA (2009) Signaling at purinergic P2X receptors. Annu Rev Physiol 71:333-359.
4. Burnstock G (2006) Pathophysiology and therapeutic potential of purinergic signaling. Pharmacol Rev 58:58-86.
5. Roberts JA, et al. (2006) Molecular properties of P2X receptors. Pflugers Arch 452: 486-500. (Pubitemid 44015086)
6. Hechler B, et al. (2003) A role of the fast ATP-gated P2X1 cation channel in thrombosis of small arteries in vivo. J Exp Med 198:661-667. (Pubitemid 37040400)
7. Tsuda M, et al. (2003) P2X4 receptors induced in spinal microglia gate tactile allodynia after nerve injury. Nature 424:778-783. (Pubitemid 37021707)
8. Coddou C, Yan Z, Obsil T, Huidobro-Toro JP, Stojilkovic SS (2011) Activation and regulation of purinergic P2X receptor channels. Pharmacol Rev 63:641-683.
9. Surprenant A, Buell G, North RA (1995) P2X receptors bring new structure to ligandgated ion channels. Trends Neurosci 18:224-229.
10. Kawate T, Michel JC, Birdsong WT, Gouaux E (2009) Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature 460:592-598.
11. Evans RJ (2010) Structural interpretation of P2X receptor mutagenesis studies on drug action. Br J Pharmacol 161:961-971.
12. Browne LE, Jiang LH, North RA (2010) New structure enlivens interest in P2X receptors. Trends Pharmacol Sci 31:229-237.
13. Young MT (2010) P2X receptors: Dawn of the post-structure era. Trends Biochem Sci 35:83-90.
14. Jiang R, et al. (2011) Agonist trapped in ATP-binding sites of the P2X2 receptor. Proc Natl Acad Sci USA 108:9066-9071.
15. Allsopp RC, El Ajouz S, Schmid R, Evans RJ (2011) Cysteine scanning mutagenesis (residues Glu52-Gly96) of the human P2X1 receptor for ATP: Mapping agonist binding and channel gating. J Biol Chem 286:29207-29217.
16. Kawate T, Robertson JL, Li M, Silberberg SD, Swartz KJ (2011) Ion access pathway to the transmembrane pore in P2X receptor channels. J Gen Physiol 137:579-590.
17. Samways DS, Khakh BS, Dutertre S, Egan TM (2011) Preferential use of unobstructed lateral portals as the access route to the pore of human ATP-gated ion channels (P2X receptors). Proc Natl Acad Sci USA 108:13800-13805.
18. Roberts JA, ValenteM, Allsopp RC, Watt D, Evans RJ (2009) Contribution of the region Glu181 to Val200 of the extracellular loop of the human P2X1 receptor to agonist binding and gating revealed using cysteine scanning mutagenesis. J Neurochem 109: 1042-1052.
19. Roberts JA, Evans RJ (2007) Cysteine substitution mutants give structural insight and identify ATP binding and activation sites at P2X receptors. J Neurosci 27:4072-4082. (Pubitemid 46597149)
20. Allsopp RC, Evans RJ (2011) The intracellular amino terminus plays a dominant role in desensitization of ATP-gated P2X receptor ion channels. J Biol Chem 286: 44691-44701.
21. Young MT, et al. (2008) Molecular shape, architecture, and size of P2X4 receptors determined using fluorescence resonance energy transfer and electron microscopy. J Biol Chem 283:26241-26251.
22. Jiang R, et al. (2010) A putative extracellular salt bridge at the subunit interface contributes to the ion channel function of the ATP-gated P2X2 receptor. J Biol Chem 285:15805-15815.