AERA_AERHY
ID AERA_AERHY Reviewed; 493 AA.
AC P09167;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 2.
DT 25-MAY-2022, entry version 131.
DE RecName: Full=Aerolysin;
DE Flags: Precursor;
GN Name=aerA;
OS Aeromonas hydrophila.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Aeromonadales;
OC Aeromonadaceae; Aeromonas.
OX NCBI_TaxID=644;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=3584074; DOI=10.1128/jb.169.6.2869-2871.1987;
RA Howard S.P., Garland W.J., Green M.J., Buckley J.T.;
RT "Nucleotide sequence of the gene for the hole-forming toxin aerolysin of
RT Aeromonas hydrophila.";
RL J. Bacteriol. 169:2869-2871(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-50.
RX PubMed=3020368; DOI=10.1007/bf00425512;
RA Howard S.P., Buckley J.T.;
RT "Molecular cloning and expression in Escherichia coli of the structural
RT gene for the hemolytic toxin aerolysin from Aeromonas hydrophila.";
RL Mol. Gen. Genet. 204:289-295(1986).
RN [3]
RP SEQUENCE REVISION.
RX PubMed=1382579; DOI=10.1021/bi00151a026;
RA van der Goot F.G., Lakey J., Pattus F., Kay C.M., Sorokine O.,
RA van Dorsselaer A., Buckley J.T.;
RT "Spectroscopic study of the activation and oligomerization of the channel-
RT forming toxin aerolysin: identification of the site of proteolytic
RT activation.";
RL Biochemistry 31:8566-8570(1992).
RN [4]
RP IMPORTANCE OF HIS-155 FOR OLIGOMERIZATION.
RX PubMed=8845373; DOI=10.1021/bi00050a028;
RA Buckley J.T., Wilmsen H.U., Lesieur C., Schulze A., Pattus F., Parker M.W.,
RA van der Goot F.G.;
RT "Protonation of histidine-132 promotes oligomerization of the channel-
RT forming toxin aerolysin.";
RL Biochemistry 34:16450-16455(1995).
RN [5]
RP FUNCTION, AND SUBUNIT.
RX PubMed=9442081; DOI=10.1074/jbc.273.4.2355;
RA Diep D.B., Nelson K.L., Raja S.M., Pleshak E.N., Buckley J.T.;
RT "Glycosylphosphatidylinositol anchors of membrane glycoproteins are binding
RT determinants for the channel-forming toxin aerolysin.";
RL J. Biol. Chem. 273:2355-2360(1998).
RN [6]
RP FUNCTION, AND SUBUNIT.
RX PubMed=10428840; DOI=10.1074/jbc.274.32.22604;
RA MacKenzie C.R., Hirama T., Buckley J.T.;
RT "Analysis of receptor binding by the channel-forming toxin aerolysin using
RT surface plasmon resonance.";
RL J. Biol. Chem. 274:22604-22609(1999).
RN [7]
RP MUTAGENESIS OF TYR-244.
RX PubMed=12219082; DOI=10.1038/nsb839;
RA Tsitrin Y., Morton C.J., el-Bez C., Paumard P., Velluz M.C., Adrian M.,
RA Dubochet J., Parker M.W., Lanzavecchia S., van der Goot F.G.;
RT "Conversion of a transmembrane to a water-soluble protein complex by a
RT single point mutation.";
RL Nat. Struct. Biol. 9:729-733(2002).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND TOPOLOGY.
RX PubMed=16424900; DOI=10.1038/sj.emboj.7600959;
RA Iacovache I., Paumard P., Scheib H., Lesieur C., Sakai N., Matile S.,
RA Parker M.W., van der Goot F.G.;
RT "A rivet model for channel formation by aerolysin-like pore-forming
RT toxins.";
RL EMBO J. 25:457-466(2006).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=7510043; DOI=10.1038/367292a0;
RA Parker M.W., Buckley J.T., Postma J.P., Tucker A.D., Leonard K., Pattus F.,
RA Tsernoglou D.;
RT "Structure of the Aeromonas toxin proaerolysin in its water-soluble and
RT membrane-channel states.";
RL Nature 367:292-295(1994).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 24-493, PROPEPTIDE, DOMAIN,
RP SUBCELLULAR LOCATION, FUNCTION, AND DISULFIDE BOND.
RX PubMed=21779171; DOI=10.1371/journal.ppat.1002135;
RA Iacovache I., Degiacomi M.T., Pernot L., Ho S., Schiltz M., Dal Peraro M.,
RA van der Goot F.G.;
RT "Dual chaperone role of the C-terminal propeptide in folding and
RT oligomerization of the pore-forming toxin aerolysin.";
RL PLoS Pathog. 7:E1002135-E1002135(2011).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 24-493 OF WILD-TYPE AND MUTANT
RP GLY-244 IN COMPLEX WITH MANNOSE-6-PHOSPHATE, DISULFIDE BOND, SUBCELLULAR
RP LOCATION, SUBUNIT, ELECTRON MICROSCOPY, FUNCTION, MUTAGENESIS OF LYS-208;
RP ASP-211; LYS-221; ARG-305; LYS-313; GLU-330; LYS-332; LYS-374 AND GLU-390,
RP AND TOPOLOGY.
RX PubMed=23912165; DOI=10.1038/nchembio.1312;
RA Degiacomi M.T., Iacovache I., Pernot L., Chami M., Kudryashev M.,
RA Stahlberg H., van der Goot F.G., Dal Peraro M.;
RT "Molecular assembly of the aerolysin pore reveals a swirling membrane-
RT insertion mechanism.";
RL Nat. Chem. Biol. 9:623-629(2013).
CC -!- FUNCTION: Secreted, cytolytic toxin that forms pores in host membranes
CC after proteolytic removal of a C-terminal propeptide, leading to
CC destruction of the membrane permeability barrier and host cell death.
CC The pores are formed by transmembrane beta-strands and are
CC approximately 3 nm in diameter. {ECO:0000269|PubMed:10428840,
CC ECO:0000269|PubMed:16424900, ECO:0000269|PubMed:21779171,
CC ECO:0000269|PubMed:23912165, ECO:0000269|PubMed:9442081}.
CC -!- SUBUNIT: Homodimer in solution; homoheptamer in the host membrane.
CC After binding to GPI-anchored proteins in target membranes and
CC proteolytic removal of the C-terminal propeptide, the protein assembles
CC into a heptameric pre-pore complex. A further conformation change leads
CC to insertion into the host membrane. {ECO:0000269|PubMed:10428840,
CC ECO:0000269|PubMed:16424900, ECO:0000269|PubMed:23912165,
CC ECO:0000269|PubMed:9442081}.
CC -!- INTERACTION:
CC P09167; P09167: aerA; NbExp=4; IntAct=EBI-8027669, EBI-8027669;
CC -!- SUBCELLULAR LOCATION: Secreted. Host cell membrane. Note=Secreted as a
CC soluble precursor.
CC -!- DOMAIN: The C-terminal propeptide is required for normal protein
CC folding and secretion; it maintains the aerolysin precursor in its
CC soluble form and prevents premature heptamerization and pore formation.
CC {ECO:0000269|PubMed:21779171}.
CC -!- PTM: Proteolytic cleavage and subsequent release of the propeptide
CC trigger a major conformation change, leading to the formation of a
CC heptameric pre-pore that then inserts into the host membrane.
CC -!- SIMILARITY: Belongs to the aerolysin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA21938.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; M16495; AAA21938.1; ALT_FRAME; Genomic_DNA.
DR EMBL; M29818; AAA21934.1; -; Genomic_DNA.
DR PIR; A25976; A25976.
DR PDB; 1PRE; X-ray; 2.80 A; A/B=24-493.
DR PDB; 1Z52; X-ray; 2.38 A; A/B=24-493.
DR PDB; 3C0M; X-ray; 2.88 A; A/B=24-493.
DR PDB; 3C0N; X-ray; 2.20 A; A/B=24-493.
DR PDB; 3C0O; X-ray; 2.50 A; A/B=24-493.
DR PDB; 3G4N; X-ray; 2.10 A; A/B=24-493.
DR PDB; 3G4O; X-ray; 2.30 A; A/B=24-493.
DR PDB; 5JZH; EM; 3.90 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N=24-447.
DR PDB; 5JZT; EM; 7.40 A; A/B/C/D/E/F/G=24-447.
DR PDB; 5JZW; EM; 4.46 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N=24-447.
DR PDBsum; 1PRE; -.
DR PDBsum; 1Z52; -.
DR PDBsum; 3C0M; -.
DR PDBsum; 3C0N; -.
DR PDBsum; 3C0O; -.
DR PDBsum; 3G4N; -.
DR PDBsum; 3G4O; -.
DR PDBsum; 5JZH; -.
DR PDBsum; 5JZT; -.
DR PDBsum; 5JZW; -.
DR AlphaFoldDB; P09167; -.
DR SMR; P09167; -.
DR DIP; DIP-42724N; -.
DR IntAct; P09167; 2.
DR MINT; P09167; -.
DR TCDB; 1.C.4.1.1; the aerolysin channel-forming toxin (aerolysin) family.
DR EvolutionaryTrace; P09167; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR Gene3D; 3.10.40.10; -; 1.
DR InterPro; IPR005831; Aerolysin/haemolysin_CS.
DR InterPro; IPR005830; Aerolysn.
DR InterPro; IPR005138; APT_dom.
DR InterPro; IPR037015; APT_N_sf.
DR InterPro; IPR016187; CTDL_fold.
DR Pfam; PF01117; Aerolysin; 1.
DR Pfam; PF03440; APT; 1.
DR PRINTS; PR00754; AEROLYSIN.
DR SMART; SM00999; Aerolysin; 1.
DR SUPFAM; SSF56436; SSF56436; 1.
DR PROSITE; PS00274; AEROLYSIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Host cell membrane; Host membrane; Membrane; Secreted; Signal; Toxin;
KW Transmembrane; Transmembrane beta strand; Virulence.
FT SIGNAL 1..23
FT CHAIN 24..445
FT /note="Aerolysin"
FT /id="PRO_0000035620"
FT PROPEP 446..493
FT /id="PRO_0000035621"
FT REGION 68..84
FT /note="Interaction with host N-linked glycan"
FT REGION 256..288
FT /note="Part of the transmembrane beta-barrel after
FT proteolytic activation of the toxin and insertion into the
FT host membrane"
FT REGION 346..355
FT /note="Interaction with glycans from host GPI-anchor"
FT SITE 155
FT /note="Important for oligomerization"
FT SITE 374
FT /note="Important for heptamerization"
FT SITE 390
FT /note="Important for heptamerization"
FT DISULFID 42..98
FT DISULFID 182..187
FT MUTAGEN 208
FT /note="K->A: No effect on heptamerization."
FT /evidence="ECO:0000269|PubMed:23912165"
FT MUTAGEN 211
FT /note="D->A: No effect on heptamerization."
FT /evidence="ECO:0000269|PubMed:23912165"
FT MUTAGEN 221
FT /note="K->A: Impairs heptamerization."
FT /evidence="ECO:0000269|PubMed:23912165"
FT MUTAGEN 244
FT /note="Y->G: Blocks the hemolytic activity. Does not affect
FT the initial structure, the ability to bind to cell-surface
FT receptors or the capacity to form heptamers. Does not
FT insert into membranes and form pores; the mutant heptamer
FT is hydrophilic instead of being hydrophobic."
FT /evidence="ECO:0000269|PubMed:12219082"
FT MUTAGEN 305
FT /note="R->A: Impairs heptamerization."
FT /evidence="ECO:0000269|PubMed:23912165"
FT MUTAGEN 313
FT /note="K->A: No effect on heptamerization."
FT /evidence="ECO:0000269|PubMed:23912165"
FT MUTAGEN 330
FT /note="E->A: No effect on heptamerization."
FT /evidence="ECO:0000269|PubMed:23912165"
FT MUTAGEN 332
FT /note="K->A: No effect on heptamerization."
FT /evidence="ECO:0000269|PubMed:23912165"
FT MUTAGEN 374
FT /note="K->A: Impairs heptamerization."
FT /evidence="ECO:0000269|PubMed:23912165"
FT MUTAGEN 390
FT /note="E->A: Nearly abolishes heptamerization."
FT /evidence="ECO:0000269|PubMed:23912165"
FT CONFLICT 277
FT /note="E -> Q (in Ref. 1; AAA21938)"
FT /evidence="ECO:0000305"
FT CONFLICT 283
FT /note="A -> R (in Ref. 1; AAA21938)"
FT /evidence="ECO:0000305"
FT CONFLICT 472
FT /note="A -> R (in Ref. 1; AAA21938)"
FT /evidence="ECO:0000305"
FT HELIX 29..31
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 33..35
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 46..48
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 51..56
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 58..62
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:3G4N"
FT TURN 74..76
FT /evidence="ECO:0007829|PDB:3C0N"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 82..84
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 94..102
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 114..116
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 121..129
FT /evidence="ECO:0007829|PDB:3G4N"
FT TURN 132..135
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 136..145
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 162..168
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:3G4N"
FT TURN 185..188
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 192..202
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 213..229
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 237..252
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 284..286
FT /evidence="ECO:0007829|PDB:3G4O"
FT HELIX 288..290
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 293..304
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 312..345
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 352..354
FT /evidence="ECO:0007829|PDB:3C0M"
FT STRAND 361..370
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 374..376
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 378..384
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 388..390
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 392..394
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 396..403
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 405..415
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 419..434
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 465..467
FT /evidence="ECO:0007829|PDB:3G4N"
FT HELIX 472..477
FT /evidence="ECO:0007829|PDB:3G4N"
FT STRAND 481..489
FT /evidence="ECO:0007829|PDB:3G4N"
SQ SEQUENCE 493 AA; 54342 MW; D396CE4EAD85AEF0 CRC64;
MQKIKLTGLS LIISGLLMAQ AQAAEPVYPD QLRLFSLGQG VCGDKYRPVN REEAQSVKSN
IVGMMGQWQI SGLANGWVIM GPGYNGEIKP GTASNTWCYP TNPVTGEIPT LSALDIPDGD
EVDVQWRLVH DSANFIKPTS YLAHYLGYAW VGGNHSQYVG EDMDVTRDGD GWVIRGNNDG
GCDGYRCGDK TAIKVSNFAY NLDPDSFKHG DVTQSDRQLV KTVVGWAVND SDTPQSGYDV
TLRYDTATNW SKTNTYGLSE KVTTKNKFKW PLVGETELSI EIAANQSWAS QNGGSTTTSL
SQSVRPTVPA RSKIPVKIEL YKADISYPYE FKADVSYDLT LSGFLRWGGN AWYTHPDNRP
NWNHTFVIGP YKDKASSIRY QWDKRYIPGE VKWWDWNWTI QQNGLSTMQN NLARVLRPVR
AGITGDFSAE SQFAGNIEIG APVPLAADSK VRRARSVDGA GQGLRLEIPL DAQELSGLGF
NNVSLSVTPA ANQ
