Functional form of Caveolin-1 is necessary for the assembly of alpha-hemolysin.
The assembly of alpha-HL was shown to rapidly progress upon its interaction with Caveolin-1. Treatment of A431 cells with alpha-HL has resulted in clustering of Caveolin-1 at cell-cell contacts. Consistent with this observation, alpha-HL mutants devoid of assembly property have not induced the clustering of Caveolin-1. While cholesterol depletion of A431 cells completely arrests the assembly of alpha-HL, chelation of membrane cholesterol results in its retarded assembly. Interestingly, HT29 cells, with low Caveolin-1 levels, are resistant to alpha-HL attack. Clustering of Caveolin-1, as seen in case of A431 cells, was readily observed in case of HT29 cells transfected with Caveolin-1 construct, thus overexpressing the full length Caveolin-1, upon alpha-HL treatment. A model was constructed to visualize the interactions between alpha-HL and Caveolin-1 which suggests that facile penetration of alpha-HL's beta-barrel might occur through protein-protein interactions with the surrounding 7 alpha-helices of Caveolin-1.
Vijayvargia
Ravi
R
National Centre for Cell Science, Ganeshkhind Road, Pune 411007, India.
Suresh
C G
CG
Krishnasastry
Musti V
MV
D020816:Amino Acid Motifs; D001427:Bacterial Toxins / Q000737:chemistry* / Q000235:genetics*; D051242:Caveolin 1; D022461:Caveolins / Q000737:chemistry* / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D007700:Kinetics; D008715:Methionine / Q000737:chemistry; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D009154:Mutation; D009761:Nystatin / Q000494:pharmacology; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D013997:Time Factors
D001427:Bacterial Toxins; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D006460:Hemolysin Proteins; D010455:Peptides; C021091:staphylococcal alpha-toxin; D009761:Nystatin; D002784:Cholesterol; D008715:Methionine