Mechanistic Insights into Gasdermin Pore Formation and Regulation in Pyroptosis

J Mol Biol. 2022 Feb 28;434(4):167297. doi: 10.1016/j.jmb.2021.167297. Epub 2021 Oct 8.

Abstract

The gasdermin family is a newly identified class of pore-forming proteins that play as the executioners of pyroptosis, a lytic pro-inflammatory type of cell death triggered by sensing cytosolic infections and danger signals. Upon activation, the gasdermin N-terminal domain translocates to the cell membrane to form pores, which allow the release of proinflammatory cytokines and alarmins, and cause cell lysis. Many structural studies have been conducted in the past few years to investigate the mechanisms of gasdermin proteins in the activation and pore formation. Here, we review these high-resolution structures and highlight the mechanistic insights into the gasdermin activation and regulation that are provided.

Keywords: GSDMA3; GSDMD; gasdermin; pore-forming protein; pyroptosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell Membrane / metabolism
  • Cytokines / metabolism
  • Humans
  • Inflammasomes / metabolism
  • Phosphate-Binding Proteins* / metabolism
  • Pore Forming Cytotoxic Proteins* / metabolism
  • Pyroptosis* / physiology

Substances

  • Cytokines
  • Inflammasomes
  • Phosphate-Binding Proteins
  • Pore Forming Cytotoxic Proteins