Difference between revisions of "Part:BBa K4165141"
 
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<partinfo>BBa_K4165141 short</partinfo>
 
<partinfo>BBa_K4165141 short</partinfo>
  
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Tau binding peptide targeting the PHF seed of Tau
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A synthetic peptide that is used for targeting misfolded tau protein (BBa_K4165009) as it binds to PHF6 (BBa_K4165204) of tau fibrils.
  
 
===Usage and Biology===
 
===Usage and Biology===
  
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MMD3 peptide sequence is DPLKARHTSVWY, it is the D-enantiomeric peptide of MM3 (BBa_K4165154). It binds to <sup>275-</sup>VQIINK<sup>-280</sup> (PHF*) and <sup>306-</sup>VQIVYK<sup>-311</sup> (PHF) motifs of tau that are reported to drive tau paired helical filament aggregates. it inhibits formation of PHF6* and full‐length Tau aggregates, but not PHF driven aggregates, and prevents the formation of tau β‐sheet‐rich fibrils.
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MMD3 peptide (DPLKARHTSVWY) acquired by mirror image phage display, it is the D-enantiomeric peptide of MM3 (BBa_K4165154). It binds to <sup>275-</sup>VQIINK<sup>-280</sup> (PHF*) and <sup>306-</sup>VQIVYK<sup>-311</sup> (PHF) motifs of tau that are reported to drive tau paired helical filament aggregates. Thus, it inhibits formation of PHF6* and full‐length Tau aggregates, but not PHF driven aggregates, and prevents the formation of tau β‐sheet‐rich fibrils.
  
 
<span class='h3bb'> <p style=" font-weight: bold; font-size:17px;"> Sequence and Features</p> </span>
 
<span class='h3bb'> <p style=" font-weight: bold; font-size:17px;"> Sequence and Features</p> </span>
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<p style=" font-weight: bold; font-size:14px;"> Modeling </p>
 
<p style=" font-weight: bold; font-size:14px;"> Modeling </p>
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MMD3 is modeled by AlphaFold2, Apptest and ITASSER, best model obtained from Apptest.  
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MMD3 was modeled by AlphaFold2, Apptest and ITASSER, and the best model was obtained from Apptest ranking 4 out of 6 according to our quality assessment code.
  
  
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/mmd3.png" style="margin-left:200px;" alt="" width="300" /></p>
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/mmd3.png" style="margin-left:300px;" alt="" width="300" /></p>
 
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                            Figure 1.: Predicted 3D structure of Synthetic peptide MMD3.
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                                Figure 1.: Predicted 3D structure of Synthetic peptide MMD3.
  
  
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/mmd3-qa.png" style="margin-left:100px;" alt="" width="800" /></p>
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/mmd3-qa.png" style="margin-left:50px;" alt="" width="800" /></p>
 
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Latest revision as of 12:28, 11 October 2022


MMD3 Peptide

A synthetic peptide that is used for targeting misfolded tau protein (BBa_K4165009) as it binds to PHF6 (BBa_K4165204) of tau fibrils.

Usage and Biology

MMD3 peptide (DPLKARHTSVWY) acquired by mirror image phage display, it is the D-enantiomeric peptide of MM3 (BBa_K4165154). It binds to 275-VQIINK-280 (PHF*) and 306-VQIVYK-311 (PHF) motifs of tau that are reported to drive tau paired helical filament aggregates. Thus, it inhibits formation of PHF6* and full‐length Tau aggregates, but not PHF driven aggregates, and prevents the formation of tau β‐sheet‐rich fibrils.

Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    COMPATIBLE WITH RFC[1000]

Dry Lab

Modeling

MMD3 was modeled by AlphaFold2, Apptest and ITASSER, and the best model was obtained from Apptest ranking 4 out of 6 according to our quality assessment code. 



                                Figure 1.: Predicted 3D structure of Synthetic peptide MMD3.


Table 1: Quality assessment parameters of MMD3 model.


References

1. Malhis, M., Kaniyappan, S., Aillaud, I., Chandupatla, R. R., Ramirez, L. M., Zweckstetter, M., ... & Funke, S. A. (2021). Potent Tau Aggregation Inhibitor D‐Peptides Selected against Tau‐Repeat 2 Using Mirror Image Phage Display. ChemBioChem, 22(21), 3049-3059.