Part:BBa_K4586030
Citrullinated vimentin
Description
It is an intermediate filament protein that is citrullinated by peptidyl arginine deiminase 2 (PAD2), which converts arginine amino acids into citrulline after translation. It has been demonstrated that citrullinated vimentin has a role in ACPA synthesis, which is a marker for numerous autoimmune diseases, specifically rheumatoid arthritis.
This figure show our Syn-Notch receptor which represent citrullinated vimentin as our ligand binding domain (LBD).
Usage
We initially used this part in our design to be the ligand binding domain in the extracellular part of our Syn notch receptor to interact with the auto-reactive B-cell receptor that secrete ACPA and transmit the signal of this selective binding inside the cell to express our therapeutic cargo within the modified exosomes that target the auto reactive B-cells.
Literature Characterization
Using sera from rheumatoid arthritis patients and healthy patients The study used gel electrophoresis and scatter diagrams to demonstrate the reactions of wild-type and mutant citrullinated vimentin.
A, There are 5 lanes containing blue staining of dodecyl sulfate-polyacrylamide gel of wild-type vimentin without peptidyl arginine deaminase treatment (lane 1), wild-type vimentin in the citrullinated form (lane 2), mutant vimentin without peptidyl arginine deaminase treatment (lane 3), and mutant vimentin in the citrullinated form (lane 4), while markers are located in lane 5. B, this is a scatter gram that demonstrates antibodies reactions against wild-type (wt), mutant (mv), and in vitro analogs (cwt,mcv). OD = optical density; NS = not significant.
characterization by mathematical modeling
This model is to compare between the types of external domains of the syn-notch receptor according to their binding to BCR based on the assumption that higher binding affinity implies lower dissociation rate.
1)We modeled the kinetics of the CV external domain of the syn-notch receptor to explain the binding affinity between it and BCR, depending on the result of the docking score, It’s concluded that it wasn’t stable and the dissociation occurs spontaneously after the binding
Graph(1) shows an increase in the free portion of CV of Syn-Notch (represented as blue line) then decreases as BCR binds to it. As the binding occurs, BCR decreases (represented as orange line) and the binding state increases (represented as green line). that dissociates after binding as it is not stable.
2)We modeled the kinetics of the CILP external domain of the syn-notch receptor to explain the binding affinity between it and BCR, depending on the result of the docking score, It’s concluded that it wasn’t stable and the dissociation occurs spontaneously after the binding.
Graph(2) shows an increase in the free portion of CILP of Syn-Notch (represented as blue line) then decreases as BCR binds to it. As the binding occurs, BCR decreases (represented as orange line) and the binding state increases (represented as green line). that dissociates after binding as it is not stable.
3)We modeled the kinetics of the CCP1 external domain of the syn-notch receptor to explain the binding affinity between it and BCR. Depending on the result of the docking score, It’s concluded that it was stable and reached steady state after binding. Which is the most suitable type in our comparison.
Graph(3) shows an increase in the free portion of CCP1 of Syn-Notch (represented as blue line) then decreases as BCR binds to it. As the binding occurs, BCR decreases (represented as orange line) and the binding state increases (represented as green line). that dissociates after binding as it is not stable.
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
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