Gasdermin-D

Function

Precursor of a pore-forming protein that plays a key role in host defense against pathogen infection and danger signals. This form constitutes the precursor of the pore-forming protein: upon cleavage, the released N-terminal moiety (Gasdermin-D, N-terminal) binds to membranes and forms pores, triggering pyroptosis.

Classification

Family (Pfam)

PF04598 Gasdermin, PF17708 Gasdermin_C

InterPro

Gasdermin, Gasdermin_pore, Gasdermin_PUB

Functional cluster

Immunoglobulin & Immune-Response Proteins

Experimental structures · PDB · 8

• 5NH1 X-ray 2.04A
• 5WQT X-ray 2.64A
• 6AO4 X-ray 2.90A
• 6KMZ X-ray 3.61A
• 6KN0 X-ray 2.79A
• 6N9O X-ray 3.50A
• 6VFE EM 3.90A
• 7Z1X X-ray 1.86A

A predicted model is available from AlphaFold.

Gene Ontology · 29

• GO:0005829 cytosol
• GO:0005576 extracellular region
• GO:0005615 extracellular space
• GO:1904813 ficolin-1-rich granule lumen
• GO:0016020 membrane
• GO:0031966 mitochondrial membrane
• GO:0072559 NLRP3 inflammasome complex
• GO:0005654 nucleoplasm
• GO:0005886 plasma membrane
• GO:0035580 specific granule lumen
• GO:1904724 tertiary granule lumen
• GO:1901612 cardiolipin binding
• GO:0070300 phosphatidic acid binding
• GO:0005546 phosphatidylinositol-4,5-bisphosphate binding
• GO:0070273 phosphatidylinositol-4-phosphate binding
• GO:0001786 phosphatidylserine binding
• GO:0022829 wide pore channel activity
• GO:0042742 defense response to bacterium
• GO:0050829 defense response to Gram-negative bacterium
• GO:0050830 defense response to Gram-positive bacterium
• GO:0006351 DNA-templated transcription
• GO:0045087 innate immune response
• GO:0046931 pore complex assembly
• GO:0050729 positive regulation of inflammatory response
• GO:0032731 positive regulation of interleukin-1 beta production
• GO:0051260 protein homooligomerization
• GO:0009306 protein secretion
• GO:0141201 pyroptotic cell death
• GO:0070269 pyroptotic inflammatory response

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Gasdermin-D 0.95
• Gasdermin-A3 0.90
• Gasdermin-A 0.89
• Gasdermin-A2 0.89
• Gasdermin-A 0.89
• Gasdermin-C 0.86
• Gasdermin-C3 0.86
• Gasdermin-B 0.86
• Gasdermin-C4 0.85
• Gasdermin-C2 0.85
• Gasdermin-C 0.85
• Gasdermin-C 0.85

Co-cited proteins · studied together in the literature

• Gasdermin-D 16 shared papers
• E3 ubiquitin-protein ligase ipaH7.8 4 shared papers
• Gasdermin-A3 4 shared papers
• Gasdermin-B 6 shared papers
• Gasdermin-E 5 shared papers
• Caspase-5 1 shared papers
• Gasdermin-A 3 shared papers
• Gasdermin-C 3 shared papers
• Genome polyprotein 1 shared papers
• MHC class II transactivator 1 shared papers
• Ninjurin-1 2 shared papers
• Ninjurin-1 2 shared papers

Literature · 45 cited papers

• The SARS-CoV-2 3CL protease inhibits pyroptosis through the cleavage of gasdermin D. Virol. Sin. · 2025
• Ubiquitination of gasdermin D N-terminal domain directs its membrane translocation and pore formation during pyroptosis. Cell Death Dis. · 2025
• ROS-dependent S-palmitoylation activates cleaved and intact gasdermin D. Nature · 2024
• The palmitoylation of gasdermin D directs its membrane translocation and pore formation during pyroptosis. Sci. Immunol. · 2024
• NU6300 covalently reacts with cysteine-191 of gasdermin D to block its cleavage and palmitoylation. Sci. Adv. · 2024
• Pyroptosis inhibiting nanobodies block Gasdermin D pore formation. Nat. Commun. · 2023
• O-GlcNAc modification of GSDMD attenuates LPS-induced endothelial cells pyroptosis. Inflamm. Res. · 2024
• Gasdermin D licenses MHCII induction to maintain food tolerance in small intestine. Cell · 2023
• Structural basis of NINJ1-mediated plasma membrane rupture in cell death. Nature · 2023
• Structural mechanisms for regulation of GSDMB pore-forming activity. Nature · 2023
• Structural basis for GSDMB pore formation and its targeting by IpaH7.8. Nature · 2023
• Insights into the GSDMB-mediated cellular lysis and its targeting by IpaH7.8. Nat. Commun. · 2023
• … and 33 more in the literature graph