P2X2 receptor subunit interfaces are missense variant hotspots, where mutations tend to increase apparent ATP affinity.

ABSTRACT:

Background and purpose

P2X receptors are trimeric ligand-gated ion channels that open a cation-selective pore in response to ATP binding to their large extracellular domain. The seven known P2X subtypes can assemble as homotrimeric or heterotrimeric complexes and contribute to numerous physiological functions, including nociception, inflammation and hearing. The overall structure of P2X receptors is well established, but little is known about the range and prevalence of human genetic variations and the functional implications of specific domains.

Experimental approach

Here, we examine the impact of P2X2 receptor inter-subunit interface missense variants identified in the human population or by structural predictions. We test both single and double mutants through electrophys

SUBMITTER: Gasparri F 

PROVIDER: S-EPMC9314836 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature