| Id |
Subject |
Object |
Predicate |
Lexical cue |
| T1 |
0-69 |
Sentence |
denotes |
Clostridium perfringens alpha-toxin recognizes the GM1a-TrkA complex. |
| T2 |
70-172 |
Sentence |
denotes |
Clostridium perfringens alpha-toxin is the major virulence factor in the pathogenesis of gas gangrene. |
| T3 |
173-360 |
Sentence |
denotes |
Alpha-toxin is a 43-kDa protein with two structural domains; the N-domain contains the catalytic site and coordinates the divalent metal ions, and the C-domain is a membrane-binding site. |
| T4 |
361-457 |
Sentence |
denotes |
The role of the exposed loop region (72-93 residues) in the N-domain, however, has been unclear. |
| T5 |
458-737 |
Sentence |
denotes |
Here we show that this loop contains a ganglioside binding motif (H … SXWY … G) that is the same motif seen in botulinum neurotoxin and directly binds to a specific conformation of the ganglioside Neu5Acα2-3(Galβ1-3GalNAcβ1-4)Galβ1-4Glcβ1Cer (GM1a) through a carbohydrate moiety. |
| T6 |
738-906 |
Sentence |
denotes |
Confocal microscopy analysis using fluorescently labeled BODIPY-GM1a revealed that the toxin colocalized with GM1a and induced clustering of GM1a on the cell membranes. |
| T7 |
907-1200 |
Sentence |
denotes |
Alpha-toxin was only slightly toxic in β1,4-N-acetylgalactosaminyltransferase knock-out mice, which lack the a-series gangliosides that contain GM1a, but was highly toxic in α2,8-sialyltransferase knock-out mice, which lack both b-series and c-series gangliosides, similar to the control mice. |
| T8 |
1201-1401 |
Sentence |
denotes |
Moreover, experiments with site-directed mutants indicated that Trp-84 and Tyr-85 in the exposed alpha-toxin loop play an important role in the interaction with GM1a and subsequent activation of TrkA. |
| T9 |
1402-1590 |
Sentence |
denotes |
These results suggest that binding of alpha-toxin to GM1a facilitates the activation of the TrkA receptor and induces a signal transduction cascade that promotes the release of chemokines. |
| T10 |
1591-1747 |
Sentence |
denotes |
Therefore, we conclude that GM1a is the primary cellular receptor for alpha-toxin, which can be a potential target for drug developed against this pathogen. |