Difference between revisions of "Part:BBa K4165204"
 
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<partinfo>BBa_K4165204 short</partinfo>
 
<partinfo>BBa_K4165204 short</partinfo>
  
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Insoluble fibers Paired Helical filaments that accumulate id Alzheimer's disease and the other tauopathies.
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Insoluble Paired Helical Filaments (PHF) accumulate in Alzheimer's disease and other tauopathies to form neurofibrillary tangles.
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===Usage and Biology===
 
===Usage and Biology===
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Tau,a microtubule-binding protein, aggregates on itself, decreasing its functionality and being closely linked totauopathies, disorders that are tau-related. Tau aggregation is also closely linked to PHF6 (VQIVYK) and PHF*, two nucleating six-residue segments (VQIINK). Our part, VQIVYK, representing residues 306 to 311 of the tau, is crucial for the full-length protein to form fibrils, and it can also do it on its own. A short sequence motif called PHF6, which may be found near the start of the third internal repeat is necessary for the assembly of tau protein into paired helical filaments (PHFs). This motif's location determines how the protein will form. The most substantial predicted-structure potential in tau is congruent with this motif. Depending on the change in propensity, point mutations in the hexapeptide region can either reduce or increase aggregation. We chose this part as a therapeutic target for AD disease by blocking an additional layer of it.
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Tau, a microtubule-binding protein, forms self-aggregations which decreases its functionality resulting in tauopathies (disorders that are tau-related). Tau aggregations are also closely linked to PHF6 (VQIVYK) and PHF* (VQIINK) which are considered the seeds for aggregation.  
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Our part, PHF, represents residues 306 to 311 found at the start of the third internal repeat of tau protein, it is essential for the formation of fibrils from full-length protein. For this reason, this seed was our main aim when targeting the tau aggregations.
  
  
 
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<span class='h3bb'>Sequence and Features</span>
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===<span class='h3bb'>Sequence and Features</span>===
 
<partinfo>BBa_K4165204 SequenceAndFeatures</partinfo>
 
<partinfo>BBa_K4165204 SequenceAndFeatures</partinfo>
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===3D Model===
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<html>
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<p><img src="https://static.igem.wiki/teams/4165/wiki/parts-registry/paired-hilical-filament.png" style="margin-left:200px;" alt="" width="500" /></p>
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</html>
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                                Figure 1.: RCSB Structure of PHF (2ON9) Visualized by Pymol.
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Latest revision as of 09:04, 13 October 2022

PHF (Paired Helical Filament)

Insoluble Paired Helical Filaments (PHF) accumulate in Alzheimer's disease and other tauopathies to form neurofibrillary tangles.

Usage and Biology

Tau, a microtubule-binding protein, forms self-aggregations which decreases its functionality resulting in tauopathies (disorders that are tau-related). Tau aggregations are also closely linked to PHF6 (VQIVYK) and PHF* (VQIINK) which are considered the seeds for aggregation.

Our part, PHF, represents residues 306 to 311 found at the start of the third internal repeat of tau protein, it is essential for the formation of fibrils from full-length protein. For this reason, this seed was our main aim when targeting the tau aggregations.


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]

3D Model

                                Figure 1.: RCSB Structure of PHF (2ON9) Visualized by Pymol.




References

1- Dammers, C., Yolcu, D., Kukuk, L., Willbold, D., Pickhardt, M., & Mandelkow, E. et al. (2016). Selection and Characterization of Tau Binding ᴅ-Enantiomeric Peptides with Potential for Therapy of Alzheimer Disease. PLOS ONE, 11(12), e0167432. doi: 10.1371/journal.pone.0167432

2- Barghorn, S., Davies, P., & Mandelkow, E. (2004). Tau Paired Helical Filaments from Alzheimer's Disease Brain and Assembled in Vitro Are Based on β-Structure in the Core Domain. Biochemistry, 43(6), 1694-1703. doi: 10.1021/bi0357006

3- von Bergen, M., Barghorn, S., Li, L., Marx, A., Biernat, J., Mandelkow, E., & Mandelkow, E. (2001). Mutations of Tau Protein in Frontotemporal Dementia Promote Aggregation of Paired Helical Filaments by Enhancing Local β-Structure. Journal Of Biological Chemistry, 276(51), 48165-48174. doi: 10.1074/jbc.m105196200

4- Ganguly, P., Do, T., Larini, L., LaPointe, N., Sercel, A., & Shade, M. et al. (2015). Tau Assembly: The Dominant Role of PHF6 (VQIVYK) in Microtubule Binding Region Repeat R3. The Journal Of Physical Chemistry B, 119(13), 4582-4593. doi: 10.1021/acs.jpcb.5b00175