Structural basis for gating mechanism of Pannexin 1 channel

Pannexin 1 (PANX1) plays extensive physiological roles across diverse fields of biology, including cell death, 1 , 2 inflammation, 3 cancer progression, 4 and neurological disorders. 5 As suggested by biochemical analysis, PANX1 forms an oligomeric channel for the facilitated diffusion of ions and large molecules across the plasma membrane upon activation. 6 However, the underlying molecular gating mechanism of PANX1 and the structure of human PANX1 are still elusive. In the current study, we report the cryo-EM structures of full-length and carboxyl-terminal (CT) tail-cleaved human PANX1. Combined with single-channel electrophysiological study, we identified the key residues involved in the gating of PANX1.