Supplementary Materials

Nidogens are therapeutic targets for the prevention of tetanus

Kinga Bercsenyi, Nathalie Schmieg, J. Barney Bryson, Martin Wallace, Paola Caccin, Matthew Golding, Giuseppe Zanotti, Linda Greensmith, Roswitha Nischt, Giampietro Schiavo

Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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  • Materials and Methods
  • Figs. S1 to S9
  • Tables S1 to S4
  • Full Reference List

Images, Video, and Other Other Media

Movie S1
Model of the interaction of HCT and nidogen-1. The crystal structure of HCT (cyan) is shown bound to the N1 peptide or to human nidogen-1 (orange). The model of the molecular complex was built and minimized as described in fig. S4.
Movie S2
Localization of nidogen-2 and HCT at the neuromuscular junction (NMJ). 3-D rendering of a NMJ from the extensor digitorum longus muscle, fixed 1 h after HCT injection, compiled from a z-stack of confocal images. Individual channels show fluorescent labeling of α-bungarotoxin (blue), combined with immunolabeling of nidogen-2 (green) and HCT (red). The merged image reveals colocalization of HCT with nidogen-2 within the NMJ. See also Fig. 2B.
Movie S3
The N1 peptide prevents TeNT-induced paralysis in vivo. Mice injected in the right triceps surae muscle with TeNT showed signs of local paralysis (the affected limb is extended) with no grip reflex. Pre-treatment of TeNT with vehicle control or the N1AA peptide had no effect on the progression of tetanic paralysis. In contrast, when mice were injected with TeNT pre-treated with the N1 peptide, they showed an overall normal posture, strong grip reflex and no gait abnormalities, demonstrating a blockade in TeNTinduced paralysis. See also Fig. 4B,C