GSDMD

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Gasdermin D (GSDMD) is a protein that in humans is encoded by the GSDMD gene. It is a member of the gasdermin family of proteins, which are involved in the process of pyroptosis, a form of programmed cell death associated with inflammation.

Structure

GSDMD is composed of two domains: an N-terminal domain and a C-terminal domain. The N-terminal domain is responsible for the pore-forming activity of the protein, while the C-terminal domain acts as an inhibitory domain that prevents the N-terminal domain from forming pores in the absence of activation signals.

Function

GSDMD plays a crucial role in the immune response by mediating pyroptosis. Upon activation by inflammatory caspases such as caspase-1, caspase-4, caspase-5, and caspase-11, the protein is cleaved into its active N-terminal fragment. This fragment then translocates to the plasma membrane, where it forms pores that lead to cell swelling, lysis, and the release of pro-inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-18 (IL-18).

Activation

The activation of GSDMD is tightly regulated by inflammatory caspases. These caspases are activated in response to various pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) that are recognized by pattern recognition receptors (PRRs) such as NOD-like receptors (NLRs) and Toll-like receptors (TLRs).

Role in Disease

Dysregulation of GSDMD and pyroptosis has been implicated in various inflammatory diseases, including sepsis, inflammatory bowel disease (IBD), and atherosclerosis. Additionally, GSDMD-mediated pyroptosis has been shown to play a role in the immune response to infections by various pathogens, including bacteria, viruses, and parasites.

Research

Ongoing research is focused on understanding the precise mechanisms of GSDMD activation and its role in disease. Therapeutic strategies targeting GSDMD and pyroptosis are being explored as potential treatments for inflammatory diseases and infections.

See also

• Pyroptosis
• Caspase
• Inflammation
• Programmed cell death