P2X₇ receptors exhibit at least three modes of allosteric antagonism.

ABSTRACT: P2X receptors are trimeric ion channels activated by adenosine triphosphate (ATP) that contribute to pathophysiological processes ranging from asthma to neuropathic pain and neurodegeneration. A number of small-molecule antagonists have been identified for these important pharmaceutical targets. However, the molecular pharmacology of P2X receptors is poorly understood because of the chemically disparate nature of antagonists and their differential actions on the seven constituent subtypes. Here, we report high-resolution cryo-electron microscopy structures of the homomeric rat P2X₇ receptor bound to five previously known small-molecule allosteric antagonists and a sixth antagonist that we identify. Our structural, biophysical, and electrophysiological data define the molecular d

SUBMITTER: Oken AC 

PROVIDER: S-EPMC11451537 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature