Crystal structure of the ATP-gated P2X4 ion channel in the closed state

By T. Kawate, J. C. Michel, William T. Birdsong, Eric Gouaux. Nature, 2009

740 citations recorded by the source corpus.

P2X receptors are cation-selective ion channels gated by extracellular ATP, and are implicated in diverse physiological processes, from synaptic transmission to inflammation to the sensing of taste and pain. Because P2X receptors are not related to other ion channel proteins of known structure, there is at present no molecular foundation for mechanisms of ligand-gating, allosteric modulation and ion permeation. Here we present crystal structures of the zebrafish P2X4 receptor in its closed, resting state. The chalice-shaped, trimeric receptor is knit together by subunit–subunit contacts implicated in ion channel gating and receptor assembly. Extracellular domains, rich in β-strands, have large acidic patches that may attract cations, through fenestrations, to vestibules near the ion channel. In the transmembrane pore, the ‘gate’ is defined by an ∼8 Å slab of protein. We define the location of three non-canonical, intersubunit ATP-binding sites, and suggest that ATP binding promotes subunit rearrangement and ion channel opening.

Subfields: Endocrine and Autonomic Systems, Physiology, Social Psychology

View Paper: https://www.semanticscholar.org/paper/ce02d887b7ea2c602c36a769c0a92f9bd61c1aa9

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Endocrine and Autonomic Systems

In Physiology

In Social Psychology

Citations in the corpus

Can I solve my structure by SAD phasing? Planning an experiment, scaling data and evaluating the useful anomalous correlation and anomalous signal (2016, neutral): “…2b78, 2fdn (Dauter et al., 1997), 2hba (Cho et al., 2014), 2o0h (Sun et al., 2007), 2prx, 2wxw (Zhou et al., 2010), 3fki (Meyer et al., 2009), 3i5d (Kawate et al., 2009), 3iko (Nagy et al., 2009), 3k9g (Abendroth et al., 2011), 3km3 (Abendroth et al., 2011), 3m6a (Duman & Löwe, 2010), 3p96…”
The P2X7 Receptor in Infection and Inflammation (2017, methodology): “Prolonged exposure to the agonist causes receptor inactivation, 18 Immunity 47, July 18, 2017 but in P2X7R (and possibly also in P2X2R and P2X4R) may also promote further increase in permeability (maybe by receptor rearrangement) with the formation of a large pore (the paradigmatic ‘‘P2X7R pore’’) t”