Gasdermin-A (Gasdermin-1) [Cleaved into: Gasdermin-A, N-terminal (GSDMA-NT); Gasdermin-A, C-terminal (GSDMA-CT)]
1_MTMFE 6_ NVTRA 11_ LARQL 16_ NPRGD 21_ LTPLD 26_ SLIDF 31_ KRFHP 36_ FCLVL 41_ RKRKS 46_ TLFWG 51_ ARYVR 56_ TDYTL 61_ LDVLE 66_ PGSSP 71_ SDPTD 76_ TGNFG 81_ FKNML 86_ DTRVE 91_ GDVDV 96_ PKTVK 101_ VKGTA 106_ GLSQN 111_ STLEV 116_ QTLSV 121_ APKAL 126_ ETVQE 131_ RKLAA 136_ DHPFL 141_ KEMQD 146_ QGENL 151_ YVVME 156_ VVETV 161_ QEVTL 166_ ERAGK 171_ AEACF 176_ SLPFF 181_ APLGL 186_ QGSIN 191_ HKEAV 196_ TIPKG 201_ CVLAF 206_ RVRQL 211_ MVKGK 216_ DEWDI 221_ PHICN 226_ DNMQT 231_ FPPGE 236_ KSGEE 241_ KVILI 246_ QASDV 251_ GDVHE 256_ GFRTL 261_ KEEVQ 266_ RETQQ 271_ VEKLS 276_ RVGQS 281_ SLLSS 286_ LSKLL 291_ GKKKE 296_ LQDLE 301_ LALEG 306_ ALDKG 311_ HEVTL 316_ EALPK 321_ DVLLS 326_ KEAVG 331_ AILYF 336_ VGALT 341_ ELSEA 346_ QQKLL 351_ VKSME 356_ KKILP 361_ VQLKL 366_ VESTM 371_ EQNFL 376_ LDKEG 381_ VFPLQ 386_ PELLS 391_ SLGDE 396_ ELTLT 401_ EALVG 406_ LSGLE 411_ VQRSG 416_ PQYMW 421_ DPDTL 426_ PRLCA 431_ LYAGL 436_SLLQQ
1: 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
2: 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)