The killer protein Gasdermin D

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The gasdermin-D pore: Executor of pyroptotic cell death

Pyroptosis is a lytic type of programmed cell death that is initiated in response to pathogenor host-derived perturbations of the cytosol. It is characterized by cell swelling, lysis, and the release of cytoplasmic content; thus restricting the replication of intracellular pathogens and attracting effector cells of the immune system. The name pyroptosis derives from the Greek pyro (fire or feve...

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Gasdermin D Exerts Anti-inflammatory Effects by Promoting Neutrophil Death

Gasdermin D (GSDMD) is considered a proinflammatory factor that mediates pyroptosis in macrophages to protect hosts from intracellular bacteria. Here, we reveal that GSDMD deficiency paradoxically augmented host responses to extracellular Escherichia coli, mainly by delaying neutrophil death, which established GSDMD as a negative regulator of innate immunity. In contrast to its activation in ma...

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Live-cell visualization of gasdermin D-driven pyroptotic cell death.

Pyroptosis is a form of cell death important in defenses against pathogens that can also result in a potent and sometimes pathological inflammatory response. During pyroptosis, GSDMD (gasdermin D), the pore-forming effector protein, is cleaved, forms oligomers, and inserts into the membranes of the cell, resulting in rapid cell death. However, the potent cell death induction caused by GSDMD has...

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Insights into Gasdermin D activation from the crystal structure of its C-terminal domain

Gasdermin D (GSDMD) is the central executioner of pyroptosis, a proinflammatory type of cell death. GSDMD is activated by the proinflammatory caspase-1 and caspase-11 via proteolytic cleavage in the linker connecting its N-terminal and Cterminal domain (GSDMDNterm, Cterm). The released N-terminal domain is sufficient to form pores in the plasma membrane, resulting in swelling and subsequent rup...

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ژورنال

عنوان ژورنال: Cell Death & Differentiation

سال: 2016

ISSN: 1350-9047,1476-5403

DOI: 10.1038/cdd.2016.100