P13128 · TACY_LISMO
- ProteinListeriolysin O
- Genehly
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids529 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
A cholesterol-dependent pore-forming toxin, which is a major virulence factor required for the escape of bacteria from phagosomal vacuoles and entry into the host cytosol. After binding to target membranes, the protein undergoes a major conformation change, leading to its insertion in the host membrane and formation of an oligomeric pore complex. Listeriolysin O activates mitogen-activated protein (MAP) kinase activity in host cells, most likely as a result of the permeabilization of the host cell membrane. Also induces a proteasome-independent degradation of UBE2I (the SUMO-conjugating enzyme UBC9) and a proteasome-dependent degradation of some sumoylated proteins. Finally, is necessary and sufficient for spacious Listeria-containing phagosomes (SLAPs) formation, suggesting a role for listeriolysin O in promoting L.monocytogenes replication in vacuoles, leading to persistent infection. Recognized by serum from healthy humans exposed to L.monocytogenes as well from patients who have recovered from listeriosis (PubMed:9284184).
Activity regulation
Activity of listeriolysin O is regulated on multiple levels. It should be high in the phagosome, thereby allowing escape of the bacteria from the phagosomal compartment. Then, once inside the host cytosol, the activity must be controlled to prevent lysis of the host plasma membrane and loss of the intracellular environment. Multiple regulatory mechanisms include translational repression, which is required to minimize levels of listeriolysin O in the host cytosol. In addition, cytolytic activity is pH-dependent. Activity is high in the acidic environment of the phagosome and is turned off in the neutral pH of the cytosol. Listeriolysin O is also ubiquitinated and rapidly degraded by host proteasome in cytosol. The lytic activity is activated by reducing agents and suppressed by oxidation. Also inhibited by very low amounts of cholesterol.
pH Dependence
Optimum pH is 5.5. Cytolytic activity is undetectable at pH 7.0.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host cell plasma membrane | |
Cellular Component | membrane | |
Molecular Function | cholesterol binding | |
Molecular Function | identical protein binding | |
Molecular Function | toxin activity | |
Biological Process | killing of cells of another organism |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Has hemolytic activity. Y406A mutant influences the pH-sensitivity.
Names & Taxonomy
Protein names
- Recommended nameListeriolysin O
- Alternative names
Gene names
- Community suggested namesListeriolysin O; LLO.
- Community suggested namesListeriolysin O; LLO.
Organism names
- Strains
- Taxonomic lineageBacteria > Bacillota > Bacilli > Bacillales > Listeriaceae > Listeria
Accessions
- Primary accessionP13128
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Host membrane ; Multi-pass membrane protein
Host cell membrane ; Multi-pass membrane protein
Note: Secreted as soluble protein that then inserts into the host membrane and forms pores formed by transmembrane beta-strands.
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 214-227 | Beta stranded | ||||
Sequence: ESQLIAKFGTAFKA | ||||||
Transmembrane | 234-243 | Beta stranded | ||||
Sequence: VNFGAISEGK | ||||||
Transmembrane | 312-321 | Beta stranded | ||||
Sequence: STKVKAAFDA | ||||||
Transmembrane | 329-341 | Beta stranded | ||||
Sequence: SGDVELTNIIKNS |
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Cells lacking this gene have severely reduced cytokine production in the mouse Listeria-infected liver cells compared to wild-type.
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 35 | in strain: F4233 / Serotype 1/2b, F5782 /Serotype 4b, F6789 / Serotype 1/2b and 12067 | ||||
Sequence: S → L | ||||||
Mutagenesis | 38-52 | 2.5-fold increase in hemolytic activity. | ||||
Sequence: Missing | ||||||
Mutagenesis | 40 | 2.5-fold increase in hemolytic activity. | ||||
Sequence: A → W | ||||||
Mutagenesis | 44 | 1500-fold decrease in virulence. | ||||
Sequence: S → A | ||||||
Mutagenesis | 44 | 2-fold increase in hemolytic activity. | ||||
Sequence: S → D or E | ||||||
Mutagenesis | 49 | Does not affect secretion and hemolytic activity. No defect in phagosomal escape. Shows a clear attenuation in virulence. | ||||
Sequence: P → A | ||||||
Mutagenesis | 50 | Does not affect secretion and hemolytic activity. Slight decrease in phagosomal escape. Shows a clear attenuation in virulence. | ||||
Sequence: K → A | ||||||
Mutagenesis | 52 | Does not affect secretion and hemolytic activity. Slight decrease in phagosomal escape. Shows a clear attenuation in virulence. | ||||
Sequence: P → A | ||||||
Mutagenesis | 175 | Loss of hemolytic activity. | ||||
Sequence: K → E | ||||||
Mutagenesis | 176 | Loss of hemolytic activity. | ||||
Sequence: S → W | ||||||
Mutagenesis | 230 | 50% hemolytic activity. | ||||
Sequence: N → W | ||||||
Mutagenesis | 262 | Loss of hemolytic activity. | ||||
Sequence: E → K | ||||||
Mutagenesis | 262 | No change in hemolytic activity. | ||||
Sequence: E → W | ||||||
Mutagenesis | 394 | 3-fold increase in hemolytic activity. | ||||
Sequence: D → W | ||||||
Natural variant | 438 | in strain: F4233 / Serotype 1/2b, F5782 /Serotype 4b, F6789 / Serotype 1/2b and 12067 | ||||
Sequence: V → I | ||||||
Mutagenesis | 461 | 10-fold increase in hemolytic activity at neutral pH, but 100-fold decrease in virulence. | ||||
Sequence: L → T | ||||||
Mutagenesis | 484 | 25% decrease in hemolytic activity, but still able to stimulate MAP kinase tyrosine phosphorylation in host cells. Does not affect membrane-binding capacity. | ||||
Sequence: C → A | ||||||
Mutagenesis | 484 | 80% decrease in hemolytic activity, but still able to stimulate MAP kinase tyrosine phosphorylation in host cells. Does not affect membrane-binding capacity. | ||||
Sequence: C → S | ||||||
Mutagenesis | 488 | Decreases toxicity by about 40%, decreases cholesterol binding by 25%. | ||||
Sequence: A → F | ||||||
Mutagenesis | 491 | 95% decrease in hemolytic activity and no stimulation of MAP kinase activity. Does not affect membrane-binding capacity. | ||||
Sequence: W → A | ||||||
Mutagenesis | 492 | 99.9% decrease in hemolytic activity and no stimulation of MAP kinase activity. Does not affect membrane-binding capacity. | ||||
Sequence: W → A | ||||||
Natural variant | 523 | in strain: F4233 / Serotype 1/2b, F5782 /Serotype 4b, F6789 / Serotype 1/2b and 12067 | ||||
Sequence: K → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 3 variants from UniProt as well as other sources including ClinVar and dbSNP.
Miscellaneous
PTM/Processing
Features
Showing features for signal, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-24 | |||||
Sequence: MKKIMLVFITLILVSLPIAQQTEA | ||||||
Chain | PRO_0000034102 | 25-529 | Listeriolysin O | |||
Sequence: KDASAFNKENSISSMAPPASPPASPKTPIEKKHADEIDKYIQGLDYNKNNVLVYHGDAVTNVPPRKGYKDGNEYIVVEKKKKSINQNNADIQVVNAISSLTYPGALVKANSELVENQPDVLPVKRDSLTLSIDLPGMTNQDNKIVVKNATKSNVNNAVNTLVERWNEKYAQAYPNVSAKIDYDDEMAYSESQLIAKFGTAFKAVNNSLNVNFGAISEGKMQEEVISFKQIYYNVNVNEPTRPSRFFGKAVTKEQLQALGVNAENPPAYISSVAYGRQVYLKLSTNSHSTKVKAAFDAAVSGKSVSGDVELTNIIKNSSFKAVIYGGSAKDEVQIIDGNLGDLRDILKKGATFNRETPGVPIAYTTNFLKDNELAVIKNNSEYIETTSKAYTDGKINIDHSGGYVAQFNISWDEVNYDPEGNEIVQHKNWSENNKSKLAHFTSSIYLPGNARNINVYAKECTGLAWEWWRTVIDDRNLPLVKNRNISIWGTTLYPKYSNKVDNPIE | ||||||
Modified residue | 44 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated. Phosphorylation does not appear to be required for ubiquitination or degradation.
Ubiquitinated.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Homooligomeric pore complex of 35-50 subunits; when inserted in the host membrane.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P13128 | hly P13128 | 4 | EBI-6407357, EBI-6407357 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 35-54 | Disordered | ||||
Sequence: SISSMAPPASPPASPKTPIE | ||||||
Motif | 483-493 | Conserved undecapeptide | ||||
Sequence: ECTGLAWEWWR | ||||||
Motif | 515-516 | Cholesterol binding | ||||
Sequence: TL |
Domain
The N-terminal region is not required for secretion and hemolytic activity, but is involved in phagosomal escape of bacteria in infected cells and is critical for bacterial virulence. This region contains a PEST-like sequence, which does not mediate proteasomal degradation, but controls listeriolysin O production in the cytosol.
Sequence similarities
Belongs to the cholesterol-dependent cytolysin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length529
- Mass (Da)58,688
- Last updated1990-01-01 v1
- Checksum83B6B0C11C033FB1
Sequence caution
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X15127 EMBL· GenBank· DDBJ | CAA33223.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M24199 EMBL· GenBank· DDBJ | AAA03018.1 EMBL· GenBank· DDBJ | Unassigned DNA | ||
X60035 EMBL· GenBank· DDBJ | CAA42639.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U25446 EMBL· GenBank· DDBJ | AAA69528.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
U25449 EMBL· GenBank· DDBJ | AAA69531.1 EMBL· GenBank· DDBJ | Genomic DNA | Different initiation | |
U25452 EMBL· GenBank· DDBJ | AAA69534.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL591974 EMBL· GenBank· DDBJ | CAD00729.1 EMBL· GenBank· DDBJ | Genomic DNA |