ID   AAPA1_HELPY             Reviewed;          30 AA.
AC   P0DUM4;
DT   29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT   29-SEP-2021, sequence version 1.
DT   25-MAY-2022, entry version 3.
DE   RecName: Full=Toxic protein AapA1;
GN   Name=aapA1 {ECO:0000303|PubMed:28077560};
GN   OrderedLocusNames=HP_1177.1 {ECO:0000305};
OS   Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori).
OC   Bacteria; Proteobacteria; Epsilonproteobacteria; Campylobacterales;
OC   Helicobacteraceae; Helicobacter.
OX   NCBI_TaxID=85962;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 700392 / 26695;
RX   PubMed=9252185; DOI=10.1038/41483;
RA   Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G.,
RA   Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A.,
RA   Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N.,
RA   Loftus B.J., Richardson D.L., Dodson R.J., Khalak H.G., Glodek A.,
RA   McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E.,
RA   Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D.,
RA   Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S.,
RA   Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C.;
RT   "The complete genome sequence of the gastric pathogen Helicobacter
RT   pylori.";
RL   Nature 388:539-547(1997).
RN   [2]
RP   FUNCTION AS A TOXIN, AND ACTIVITY REGULATION.
RC   STRAIN=ATCC 700392 / 26695;
RX   PubMed=28077560; DOI=10.1093/nar/gkw1343;
RA   Arnion H., Korkut D.N., Masachis Gelo S., Chabas S., Reignier J., Iost I.,
RA   Darfeuille F.;
RT   "Mechanistic insights into type I toxin antitoxin systems in Helicobacter
RT   pylori: the importance of mRNA folding in controlling toxin expression.";
RL   Nucleic Acids Res. 45:4782-4795(2017).
RN   [3]
RP   FUNCTION AS A TOXIN, SUBCELLULAR LOCATION, AND INDUCTION.
RC   STRAIN=ATCC 700392 / 26695;
RX   PubMed=33229580; DOI=10.1073/pnas.2016195117;
RA   El Mortaji L., Tejada-Arranz A., Rifflet A., Boneca I.G.,
RA   Pehau-Arnaudet G., Radicella J.P., Marsin S., De Reuse H.;
RT   "A peptide of a type I toxin-antitoxin system induces Helicobacter pylori
RT   morphological transformation from spiral shape to coccoids.";
RL   Proc. Natl. Acad. Sci. U.S.A. 117:31398-31409(2020).
RN   [4] {ECO:0007829|PDB:6GIF, ECO:0007829|PDB:6GIG}
RP   STRUCTURE BY NMR, FUNCTION AS A TOXIN, FUNCTION IN STRESS RESPONSE,
RP   SUBCELLULAR LOCATION, DOMAIN, LIPID-BINDING, AND MUTAGENESIS OF
RP   1-MET--ASN-8; TRP-10; TYR-14; LEU-15; LYS-16; PHE-19; GLY-21; LYS-23;
RP   VAL-26; 29-LYS-ARG-30 AND ARG-30.
RC   STRAIN=ATCC 700392 / 26695;
RX   PubMed=31476357; DOI=10.1016/j.bbagen.2019.129423;
RA   Korkut D.N., Alves I.D., Vogel A., Chabas S., Sharma C.M., Martinez D.,
RA   Loquet A., Salgado G.F., Darfeuille F.;
RT   "Structural insights into the AapA1 toxin of Helicobacter pylori.";
RL   Biochim. Biophys. Acta 1864:129423-129423(2020).
CC   -!- FUNCTION: May be involved in response to oxidative stress (Probable).
CC       Toxic component of a type I toxin-antitoxin (TA) system. When
CC       overexpression is induced in situ in the absence of its cognate
CC       antisense RNA antitoxin IsoA1 it leads to cell growth arrest and cell
CC       death without lysis. Neutralized by IsoA1 RNA which forms an extensive
CC       duplex with the mRNA (PubMed:28077560, PubMed:33229580,
CC       PubMed:31476357). Binds artificial prokaryotic and eukaryotic lipid
CC       membranes, with 30-fold higher affinity for prokaryotic membranes.
CC       Molecular dynamics suggests the peptide penetrates the membrane leading
CC       to lipid reorganization and thinning of the bilayer (PubMed:31476357).
CC       Induction of toxin in the absence of antitoxin RNA causes a fast
CC       conversion of cells from spiral-shaped to coccoid forms; cells have no
CC       visible membrane defects and resemble wild-type 'aging coccoids'. Toxin
CC       causes a moderate decrease in membrane potential and ATP content and
CC       alterations in peptidoglycan muropeptide abundance; GlcNAc-MurNAc
CC       dipeptides increase while GlcNAc-MurNAc tripeptides decrease (i.e. a
CC       faster phenocopy of cell aging). Deletion of all 6 AapA/IsoA TA loci in
CC       strain B128 leads to slower than wild-type conversion of H2O2-treated
CC       cells to the coccoid form. This suggests oxidative stress triggers
CC       coccoid transformation via these type I TA systems, although other
CC       factors eventually drive the morphology change (PubMed:33229580).
CC       {ECO:0000269|PubMed:28077560, ECO:0000269|PubMed:31476357,
CC       ECO:0000269|PubMed:33229580, ECO:0000305|PubMed:33229580}.
CC   -!- ACTIVITY REGULATION: Transcription of the aapA1 gene generates a full-
CC       length transcript whose folding impedes translation. Processing of the
CC       3' end of the aapA1 message generates a shorter transcript that becomes
CC       translatable after a structural rearrangement. The processing also
CC       makes it more susceptible to forming dsRNA with IsoA1 which leads to
CC       duplex RNA degradation by RNase 3 (rnc). {ECO:0000269|PubMed:28077560}.
CC   -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000305|PubMed:31476357,
CC       ECO:0000305|PubMed:33229580}.
CC   -!- INDUCTION: Constitutively expressed, increases slightly as cells get
CC       older. Does not respond to acid, rifampicin, tetracycline or Ni(2+)
CC       stress. Antisense RNA expression decreases strongly under oxidative
CC       stress (H2O2 or paraquat), while aapA1 expression decreases only
CC       marginally in H2O2 but decreases strongly in response to paraquat. A
CC       decrease in antisense RNA leads to an increase in toxin production.
CC       {ECO:0000269|PubMed:33229580}.
CC   -!- DOMAIN: Has 3 regions; the N-terminal 8 residues are disordered and not
CC       required for toxicity, the central helical segment (residues 9-28)
CC       probably crosses the membrane, and the charged C-terminal 2 residues
CC       which are required for toxicity. {ECO:0000269|PubMed:31476357}.
CC   -!- MISCELLANEOUS: Addition of an SPA-tag or GFP to the C-terminus of the
CC       protein renders it non-toxic, but detectable by antibodies.
CC       {ECO:0000269|PubMed:31476357, ECO:0000269|PubMed:33229580}.
CC   -!- MISCELLANEOUS: As Helicobacter ages cells change from a helicoidal
CC       shape with multiple flagella at one pole to coccoid forms by 70 hours
CC       in culture. As they age peptidoglycan muropeptide abundance alters;
CC       GlcNAc-MurNAc dipeptides increase while GlcNAc-MurNAc tripeptides
CC       decrease. {ECO:0000269|PubMed:33229580}.
CC   -!- SIMILARITY: Belongs to the AapA toxin family. {ECO:0000305}.
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DR   EMBL; AE000511; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   PDB; 6GIF; NMR; -; A=1-30.
DR   PDB; 6GIG; NMR; -; A=1-30.
DR   PDBsum; 6GIF; -.
DR   PDBsum; 6GIG; -.
DR   SMR; P0DUM4; -.
DR   Proteomes; UP000000429; Chromosome.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR   GO; GO:0008360; P:regulation of cell shape; IEA:UniProtKB-KW.
PE   1: Evidence at protein level;
KW   3D-structure; Cell inner membrane; Cell membrane; Cell shape;
KW   Lipid-binding; Membrane; Reference proteome; Stress response;
KW   Toxin-antitoxin system.
FT   CHAIN           1..30
FT                   /note="Toxic protein AapA1"
FT                   /id="PRO_0000453284"
FT   MUTAGEN         1..8
FT                   /note="Missing: Toxic."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         10
FT                   /note="W->A: Reduced toxicity."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         14
FT                   /note="Y->A: Reduced toxicity."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         15
FT                   /note="L->A: Reduced toxicity."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         16
FT                   /note="K->A: Reduced toxicity."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         19
FT                   /note="F->A: Reduced toxicity."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         21
FT                   /note="G->A: No longer toxic."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         23
FT                   /note="K->A: Reduced toxicity."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         26
FT                   /note="V->A: Reduced toxicity."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         29..30
FT                   /note="Missing: No longer toxic."
FT                   /evidence="ECO:0000269|PubMed:31476357"
FT   MUTAGEN         30
FT                   /note="Missing: Reduced toxicity."
FT                   /evidence="ECO:0000269|PubMed:31476357"
SQ   SEQUENCE   30 AA;  3463 MW;  864CF81C950C0891 CRC64;
     MATKHGKNSW KTLYLKISFL GCKVVVLLKR