GSDMA
Domain
Intramolecular interactions between N- and C-terminal domains are important for autoinhibition in the absence of activation signal. The intrinsic pyroptosis-inducing activity is carried by the N-terminal domain.
Function
Gasdermin-A
This form constitutes the precursor of the pore-forming protein and acts as a sensor of infection: upon infection by S.pyogenes, specifically cleaved by S.pyogenes effector protein SpeB in epithelial cells, releasing the N-terminal moiety (Gasdermin-A, N-terminal) that binds to membranes and forms pores, triggering pyroptosis.
Gasdermin-A, N-terminal
Pore-forming protein that causes membrane permeabilization and pyroptosis (PubMed:17471240, PubMed:27281216, PubMed:35110732, PubMed:35545676). Released upon cleavage by S.pyogenes effector protein SpeB, and binds to membrane inner leaflet lipids (PubMed:27281216, PubMed:35110732, PubMed:35545676). Homooligomerizes within the membrane and forms pores of 10-15 nanometers (nm) of inner diameter, triggering pyroptosis (PubMed:27281216, PubMed:35110732, PubMed:35545676). Pyroptosis triggers the elimination of the infected skin cell, depriving the pathogen of its protective niche, while inducing an inflammatory response (PubMed:35110732, PubMed:35545676). This ultimately prevents bacterial penetration of the epithelial barrier and a subsequent systemic dissemination of the pathogen (PubMed:35110732, PubMed:35545676). Binds to cardiolipin and other acidic phospholipids, such as phosphatidylserine, which mediate its targeting to the inner leaflet membrane (PubMed:27281216, PubMed:35110732).
Post-translational modifications
Cleavage by S.pyogenes SpeB relieves autoinhibition by releasing the N-terminal moiety (Gasdermin-A, N-terminal) that initiates pyroptosis.
Palmitoylated.
Sequence Similarities
Belongs to the gasdermin family.
Tissue Specificity
Expressed predominantly in the gastrointestinal tract and, at a lower level, in the skin. Also detected in mammary gland. In the gastrointestinal tract, mainly expressed in differentiated cells, including the differentiated cell layer of esophagus and mucus-secreting pit cells of the gastric epithelium. Down-regulated in gastric cancer cells.
Cellular localization
- Gasdermin-A
- Cytoplasm
- Perinuclear region
- Cytoplasm
- Cytosol
- Gasdermin-A, N-terminal
- Cell membrane
- Multi-pass membrane protein
Alternative names
GSDM, GSDM1, FKSG9, GSDMA, Gasdermin-A, Gasdermin-1