GSDM_RUNZN
ID GSDM_RUNZN Reviewed; 268 AA.
AC P0DV48;
DT 25-MAY-2022, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 1.
DT 03-AUG-2022, entry version 2.
DE RecName: Full=Gasdermin bGSDM {ECO:0000305};
DE Short=bGSDM {ECO:0000303|PubMed:35025633};
DE AltName: Full=Bacterial gasdermin {ECO:0000303|PubMed:35025633};
DE Contains:
DE RecName: Full=Gasdermin bGSDM, N-terminus {ECO:0000305};
GN ORFNames=G563DRAFT_02010 {ECO:0000303|PubMed:35025633};
OS Runella zeae (strain ATCC BAA-293 / DSM 19591 / LMG 21438 / NS12).
OC Bacteria; Bacteroidetes; Cytophagia; Cytophagales; Spirosomaceae; Runella.
OX NCBI_TaxID=1123078;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC BAA-293 / DSM 19591 / LMG 21438 / NS12;
RA Kyrpides N., Huntemann M., Han J., Chen A., Mavromatis K., Markowitz V.,
RA Palaniappan K., Ivanova N., Schaumberg A., Pati A., Liolios K.,
RA Nordberg H.P., Cantor M.N., Hua S.X., Woyke T.;
RL Submitted (JUL-2013) to the EMBL/GenBank/DDBJ databases.
RN [2] {ECO:0007744|PDB:7N52}
RP X-RAY CRYSTALLOGRAPHY (2.90 ANGSTROMS) OF 2-268, FUNCTION, ACTIVITY
RP REGULATION, SUBUNIT, SUBCELLULAR LOCATION, MASS SPECTROMETRY,
RP PALMITOYLATION AT CYS-3, AND MUTAGENESIS OF CYS-3; ASN-244; ARG-245;
RP VAL-246; LEU-247; 248-GLY--THR-268; GLY-248; GLU-249; ASN-250 AND MET-251.
RC STRAIN=ATCC BAA-293 / DSM 19591 / LMG 21438 / NS12;
RX PubMed=35025633; DOI=10.1126/science.abj8432;
RA Johnson A.G., Wein T., Mayer M.L., Duncan-Lowey B., Yirmiya E.,
RA Oppenheimer-Shaanan Y., Amitai G., Sorek R., Kranzusch P.J.;
RT "Bacterial gasdermins reveal an ancient mechanism of cell death.";
RL Science 375:221-225(2022).
CC -!- FUNCTION: [Gasdermin bGSDM]: Precursor of a pore-forming protein
CC involved in defense against bacteriophages (By similarity). Cleavage of
CC this precursor by its dedicated, neighboring protease (G563DRAFT_02009)
CC releases the active moiety (gasdermin bGSDM, N-terminus) which inserts
CC into membranes, forming pores and triggering cell death
CC (PubMed:35025633). Expression of bGSDM and its protease is highly toxic
CC in E.coli (PubMed:35025633). Cells expressing the gene pair stop
CC dividing and lose membrane integrity (PubMed:35025633). Both proteins
CC are required to kill E.coli (PubMed:35025633).
CC {ECO:0000250|UniProtKB:A0A0S2DNG5, ECO:0000269|PubMed:35025633}.
CC -!- FUNCTION: [Gasdermin bGSDM, N-terminus]: Pore-forming protein that
CC causes membrane permeabilization via a pyroptosis-like activity
CC (PubMed:35025633). Makes ring-like pores with walls about 50 Angstroms
CC thick and an interior pore diameter of 200-300 Angstroms, when
CC integrated in liposomes (PubMed:35025633).
CC {ECO:0000269|PubMed:35025633}.
CC -!- ACTIVITY REGULATION: [Gasdermin bGSDM]: The full-length protein before
CC cleavage is inactive: intramolecular interactions between the N-
CC terminal domain and the C-terminal region, as well as the lipid
CC modification, mediate autoinhibition (PubMed:35025633). The pyroptosis-
CC like-inducing activity is carried by the released N-terminal domain
CC (gasdermin bGSDM, N-terminus) (PubMed:35025633).
CC {ECO:0000269|PubMed:35025633}.
CC -!- SUBUNIT: [Gasdermin bGSDM]: Monomer in solution.
CC {ECO:0000269|PubMed:35025633}.
CC -!- SUBUNIT: [Gasdermin bGSDM, N-terminus]: Forms large, probably
CC homooligomeric ring-shaped pores when inserted in membranes.
CC {ECO:0000269|PubMed:35025633}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin bGSDM]: Cytoplasm
CC {ECO:0000269|PubMed:35025633}.
CC -!- SUBCELLULAR LOCATION: [Gasdermin bGSDM, N-terminus]: Cell inner
CC membrane {ECO:0000269|PubMed:35025633}; Multi-pass membrane protein
CC {ECO:0000305}. Note=Upon proteolysis the protein forms membrane-
CC associated puncta. {ECO:0000269|PubMed:35025633}.
CC -!- DOMAIN: The N-terminus has marked structural similarity to the
CC mammalian gasdermin N-terminal domain. The C-terminal region wraps
CC around the twisted beta sheet core, probably stabilizing the inactive
CC state. The C-terminal region can assume multiple conformations.
CC {ECO:0000269|PubMed:35025633}.
CC -!- PTM: [Gasdermin bGSDM]: Cleavage by the adjacently encoded protease
CC (G563DRAFT_02009) between Leu-247 and Gly-248 relieves autoinhibition,
CC releasing the N-terminus which initiates loss of cell integrity.
CC {ECO:0000269|PubMed:35025633}.
CC -!- PTM: Palmitoylation helps stabilize the inactive state; may self-
CC palmitoylate. Palmitoylation is not required for permeabilization of
CC liposomes by the ring-like pores in vitro.
CC {ECO:0000269|PubMed:35025633}.
CC -!- MASS SPECTROMETRY: Mass=28228.49; Method=Electrospray; Note=Gasdermin
CC bGSDM, N-terminus, palmitoylated.;
CC Evidence={ECO:0000269|PubMed:35025633};
CC -!- MASS SPECTROMETRY: Mass=30284.94; Method=Electrospray; Note=Full-
CC length, unmodified protein expressed in E.coli.;
CC Evidence={ECO:0000269|PubMed:35025633};
CC -!- MASS SPECTROMETRY: Mass=30523.41; Method=Electrospray; Note=Full-
CC length, palmitoylated protein expressed in E.coli.;
CC Evidence={ECO:0000269|PubMed:35025633};
CC -!- MASS SPECTROMETRY: Mass=30549.07; Method=Electrospray; Note=Full-
CC length, modified protein expressed in E.coli.;
CC Evidence={ECO:0000269|PubMed:35025633};
CC -!- SIMILARITY: Belongs to the bacterial gasdermin family.
CC {ECO:0000269|PubMed:35025633}.
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DR EMBL; AUIF01000011; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PDB; 7N52; X-ray; 1.67 A; A/B/C/D=2-268.
DR PDBsum; 7N52; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
PE 1: Evidence at protein level;
KW 3D-structure; Antiviral defense; Cell inner membrane; Cell membrane;
KW Cytoplasm; Lipoprotein; Membrane; Palmitate; Transmembrane;
KW Transmembrane beta strand.
FT CHAIN 1..268
FT /note="Gasdermin bGSDM"
FT /id="PRO_0000455572"
FT CHAIN 1..247
FT /note="Gasdermin bGSDM, N-terminus"
FT /evidence="ECO:0000269|PubMed:35025633"
FT /id="PRO_0000455573"
FT REGION 248..268
FT /note="C-terminal region"
FT /evidence="ECO:0000269|PubMed:35025633"
FT SITE 247..248
FT /note="Cleavage; by protease G563DRAFT_02009"
FT /evidence="ECO:0000269|PubMed:35025633"
FT LIPID 3
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 3
FT /note="C->A: Protein is less thermostable, operon is no
FT longer toxic in E.coli, protein is partially cleaved by
FT neighboring protease, still forms membrane puncta in
FT liposomes which are less leaky than wild-type in vitro."
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 244
FT /note="N->A: Reduced cleavage, still toxic."
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 245
FT /note="R->A: Reduced cleavage, still toxic."
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 246
FT /note="V->A: Reduced cleavage, still toxic."
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 247
FT /note="L->A: No longer cleaved by protease, non-toxic,
FT liposomes incubated with bGSDM do not leak."
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 248..268
FT /note="Missing: Increased cell growth arrest upon
FT induction, toxic in the absence of protease."
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 248
FT /note="G->A: No longer cleaved by protease, non-toxic."
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 249
FT /note="E->A: Cleaved by protease, reduced toxicity."
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 250
FT /note="N->A: Partially cleaved by protease, non-toxic."
FT /evidence="ECO:0000269|PubMed:35025633"
FT MUTAGEN 251
FT /note="M->A: Cleaved by protease, non-toxic."
FT /evidence="ECO:0000269|PubMed:35025633"
SQ SEQUENCE 268 AA; 30330 MW; 9574005259E8769E CRC64;
MECNDPFVVA LKDKGYSLVA YPKTSIRPLH IYEHTIKNAF KRIWIQSEAQ PTSGFIKSLF
SDKIHGAIGL SDGQGIDIDL RKTNSLSSAV AAKILESYFQ DSAPSFDLAF ENSSSVIFHI
EEIITTDADE ISLRNWLNDN QNELREIYKE EIKKGNFFVA TSLLRAKKMR MQFERKNKGE
LGVDVSKIKN LPVDAKLESK IEGSTYDRLV FETPDEGIVF GVKLVRLFFS DNGILTIDKK
QDFNRVLGEN MALNLFTEIQ DAGFIEVT
