Part:BBa_K4165204
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.
3D Model
Figure 1.: RCSB Structure of PHF (2ON9)
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]
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
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