View source for Aerolysin

{{Short description|Pore-forming toxin of Aeromonas hydrophila, used as a nanopore for short oligonucleotides and peptides}}
{{Infobox protein
| name = Aerolysin
| organism = ''Aeromonas hydrophila''
| symbol = ''aerA'' (UniProt P09167)
| structure_pdb = 5JZT
| pore_diameter = Narrow; the sensing region spans 0.5 to 1.5 nm in engineered variants. Length about 10 nm
| subunits = 7 (homoheptamer; two concentric β-barrels)
| function = Pore-forming toxin; wild-type pore used as a single-molecule sensor
}}
'''Aerolysin''' is a toxin made by the bacterium ''Aeromonas hydrophila'', a species associated with diarrheal disease and deep wound infections.<ref name="parker">{{cite journal |last1=Parker |first1=M. W. |last2=et al. |title=Structure of the ''Aeromonas'' toxin proaerolysin in its water-soluble and membrane-channel states |journal=Nature |volume=367 |issue=6460 |pages=292-295 |year=1994 |doi=10.1038/367292a0}}</ref> It is secreted as a soluble protein. On a target cell, seven copies join into a narrow channel through the membrane, and the cell loses its contents. In the laboratory the same channel, set in a lipid bilayer, is used as a [[biological nanopore]]: it resolves oligonucleotides that differ by a single base and peptides that differ by a single amino acid.

== Toxin ==
The name comes from a paper of 1974 on a hemolytic substance in the culture fluid of ''A. hydrophila''. The authors purified it by salt fractionation and gel filtration, estimated its molecular weight at 50,000 and wrote that it was "here termed 'aerolysin'".<ref name="bernheimer">{{cite journal |last1=Bernheimer |first1=A. W. |last2=Avigad |first2=L. S. |title=Partial characterization of aerolysin, a lytic exotoxin from ''Aeromonas hydrophila'' |journal=Infection and Immunity |volume=9 |issue=6 |pages=1016-1021 |year=1974 |doi=10.1128/iai.9.6.1016-1021.1974}}</ref>

A gene named ''aerA'' codes for a chain of 493 residues. A signal peptide of 23 residues is removed on export, and what remains is proaerolysin, a protein of about 52,000 daltons that occurs as a dimer.<ref name="uniprot">{{cite web |url=https://www.uniprot.org/uniprotkb/P09167 |title=P09167: Aerolysin, ''Aeromonas hydrophila'' |publisher=UniProt |access-date=October 25, 2026}}</ref> Proaerolysin binds proteins that hang on the outer face of a cell membrane by a glycosylphosphatidylinositol anchor.<ref name="diep">{{cite journal |last1=Diep |first1=D. B. |last2=et al. |title=Glycosylphosphatidylinositol anchors of membrane glycoproteins are binding determinants for the channel-forming toxin aerolysin |journal=Journal of Biological Chemistry |volume=273 |issue=4 |pages=2355-2360 |year=1998 |doi=10.1074/jbc.273.4.2355}}</ref> Then a protease of the host such as furin cuts a loop near the C terminus after an arginine, and only the cut protein can form oligomers and channels.<ref name="abrami">{{cite journal |last1=Abrami |first1=L. |last2=et al. |title=The pore-forming toxin proaerolysin is activated by furin |journal=Journal of Biological Chemistry |volume=273 |issue=49 |pages=32656-32661 |year=1998 |doi=10.1074/jbc.273.49.32656}}</ref> A ring of seven cut molecules is the prepore. It inserts into the membrane as a β-barrel, which leaves a channel through the wall of the cell.

== Structure ==
The first structure, of the proaerolysin precursor, came from X-ray crystallography at 2.8 Å resolution in 1994. The fold had not been seen before. Electron micrographs of the oligomer gave the authors enough to build a model of the membrane channel.<ref name="parker" /> In 2016 cryo-electron microscopy gave structures of three intermediates and of the finished pore. The pore consists of two concentric β-barrels held together by hydrophobic contacts, a fold the authors link to the "prion-like ultrastability" of the channel. Aerolysin is the founding member of a family of pore-forming toxins found in all kingdoms of life.<ref name="iacovache">{{cite journal |last1=Iacovache |first1=I. |last2=et al. |title=Cryo-EM structure of aerolysin variants reveals a novel protein fold and the pore-formation process |journal=Nature Communications |volume=7 |pages=12062 |year=2016 |doi=10.1038/ncomms12062}}</ref>

Aerolysin differs from the other pores in use mainly by its length. A 2019 study put it at about 10 nm, against about 8.5 nm for [[alpha-hemolysin]] and about 8.0 nm for [[MspA]], and noted that the greater length together with a narrower bore slows a molecule down without help from a motor or an adapter. By mutating residues at the sensing region, near positions 220 and 238, the authors varied the sensing diameter from 5 Å to 15 Å.<ref name="cao2019">{{cite journal |last1=Cao |first1=C. |last2=et al. |title=Single-molecule sensing of peptides and nucleic acids by engineered aerolysin nanopores |journal=Nature Communications |volume=10 |pages=4918 |year=2019 |doi=10.1038/s41467-019-12690-9}}</ref> Alpha-hemolysin is 1.4 nm wide at its narrowest point.

== As a nanopore ==
Alpha-hemolysin gave the first single strands of DNA in 1996, and aerolysin received much less attention as a sensor. In 2016 a group showed that a wild-type aerolysin pore, with no motor enzyme and no engineering, could separate oligonucleotides of 2 to 10 bases from one another, tell them apart in a mixture and follow exonuclease I as it cut a strand step by step.<ref name="cao">{{cite journal |last1=Cao |first1=C. |last2=et al. |title=Discrimination of oligonucleotides of different lengths with a wild-type aerolysin nanopore |journal=Nature Nanotechnology |volume=11 |issue=8 |pages=713-718 |year=2016 |doi=10.1038/nnano.2016.66}}</ref>

Peptides followed. The wild-type pore separated short homopeptides, mixed in solution, that differed in length by one amino acid, and it found a few dozen impurities in a commercial peptide sample of high purity.<ref name="piguet">{{cite journal |last1=Piguet |first1=F. |last2=et al. |title=Identification of single amino acid differences in uniformly charged homopolymeric peptides with aerolysin nanopore |journal=Nature Communications |volume=9 |pages=966 |year=2018 |doi=10.1038/s41467-018-03418-2}}</ref> In 2020, with a short polycationic carrier attached, all twenty proteinogenic amino acids gave a signal, and 13 of them could be identified by their current blockades, a result the authors suggest may lead toward [[nanopore protein sequencing]]. In simulations, a carrier-bound amino acid stayed inside the sensing region of the pore for long enough to be measured.<ref name="ouldali">{{cite journal |last1=Ouldali |first1=H. |last2=et al. |title=Electrical recognition of the twenty proteinogenic amino acids using an aerolysin nanopore |journal=Nature Biotechnology |volume=38 |issue=2 |pages=176-181 |year=2020 |doi=10.1038/s41587-019-0345-2}}</ref>

== At Molecular Reality ==
[[JeoPOREdy!]], the company's quiz game, has a category called Aerolysin Alley. It contains one clue, and the answer is "What is aerolysin?" The clue says that two research groups turned the ''Aeromonas hydrophila'' pore into "a champion sensor, even though in nature it punches holes in your gut cells".<ref name="records">{{cite web |title=Company records |publisher=Molecular Reality Corporation |date=October 2026}}</ref>

== See also ==
* [[Alpha-hemolysin]]
* [[Biological nanopore]]
* [[Nanopore protein sequencing]]
* [[JeoPOREdy!]]

== References ==
{{Reflist}}

{{Nanopores}}

[[Category:Nanopores]]
[[Category:Pore-forming toxins]]
[[Category:Bacterial toxins]]