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Sites of Tau Important for Aggregation Populate β-Structure and Bind to Microtubules and Polyanions
Open accessAbstract
The aggregation of the microtubule-associated tau protein and formation of “neurofibrillary tangles” is one of the hallmarks of Alzheimer disease. The mechanisms underlying the structural transition of innocuous, natively unfolded tau to neurotoxic forms and the detailed mechanisms of binding to microtubules are largely unknown. Here we report the high-resolution characterization of the repeat domain of soluble tau using multidimensional NMR spectroscopy. NMR secondary chemical shifts detect residual β-structure for 8–10 residues at the beginning of repeats R2–R4. These regions correspond to sequence motifs known to form the core of the cross-β-structure of tau-paired helical filaments. Chemical shift perturbation studies show that polyanions, which promote paired helical filament aggregation, as well as microtubules interact with tau through positive charges near the ends of the repeats and through the β-forming motifs at the beginning of repeats 2 and 3. The high degree of similarity between the binding of polyanions and microtubules supports the hypothesis that stable microtubules prevent paired helical filament formation by blocking the tau-polyanion interaction sites, which are crucial for paired helical filament formation. The aggregation of the microtubule-associated tau protein and formation of “neurofibrillary tangles” is one of the hallmarks of Alzheimer disease. The mechanisms underlying the structural transition of innocuous, natively unfolded tau to neurotoxic forms and the detailed mechanisms of binding to microtubules are largely unknown. Here we report the high-resolution characterization of the repeat domain of soluble tau using multidimensional NMR spectroscopy. NMR secondary chemical shifts detect residual β-structure for 8–10 residues at the beginning of repeats R2–R4. These regions correspond to sequence motifs known to form the core of the cross-β-structure of tau-paired helical filaments. Chemical shift perturbation studies show that polyanions, which promote paired helical filament aggregation, as well as microtubules interact with tau through positive charges near the ends of the repeats and through the β-forming motifs at the beginning of repeats 2 and 3. The high degree of similarity between the binding of polyanions and microtubules supports the hypothesis that stable microtubules prevent paired helical filament formation by blocking the tau-polyanion interaction sites, which are crucial for paired helical filament formation. Alzheimer disease is characterized by abnormal protein deposits in the brain, such as amyloid plaques or neurofibrillary tangles, formed by fibrous assemblies of the Aβ peptide (1Selkoe D.J. Schenk D. Annu. Rev. Pharmacol. Toxicol. 2003; 43: 545-584Crossref PubMed Scopus (754) Google Scholar) or of the microtubule (MT) 1The abbreviations used are: MT, microtubule; PHF, paired helical filament; MES, 4-morpholineethanesulfonic acid; Pipes, 1,4-piperazinediethanesulfonic acid; HSQC, heteronuclear single quantum correlation. -associated tau protein (2Mandelkow E.M. Mandelkow E. Trends Cell Biol. 1998; 8: 425-427Abstract Full Text Full Text PDF PubMed Scopus (445) Google Scholar). These aggregates are thought to be toxic to neurons, either by causing some toxic signaling defect or by obstructing the cell interior. Therefore, one of the top priorities in Alzheimer research is to understand the reasons for the pathological aggregation and to find methods to prevent it. Although the structural principles governing Aβ aggregation are known in some detail, little is known for the tau protein. Tau is a microtubule-associated protein that regulates MT stability, neurite outgrowth, and other MT-dependent functions. The three or four repeats in the C-terminal half of the protein and the flanking proline-rich basic domains are known to be involved in MT binding (3Gustke N. Trinczek B. Biernat J. Mandelkow E.M. Mandelkow E. Biochemistry. 1994; 33: 9511-9522Crossref PubMed Scopus (547) Google Scholar). The affinity is regulated by phosphorylation particularly at KXGS-motifs in the repeats (4Biernat J. Gustke N. Drewes G. Mandelkow E.M. Mandelkow E. Neuron. 1993; 11: 153-163Abstract Full Text PDF PubMed Scopus (662) Google Scholar). Interestingly the same phosphorylation sites have an inhibitory influence on aggregation (5Schneider A. Biernat J. von Bergen M. Mandelkow E. Mandelkow E.M. Biochemistry. 1999; 38: 3549-3558Crossref PubMed Scopus (460) Google Scholar). Unbound tau can assemble into Alzheimer-like paired helical filaments (PHFs) whose polymerization can be enhanced by oxidation of SH groups and by polyanions (e.g. heparin, poly-Glu (6Barghorn S. Mandelkow E. Biochemistry. 2002; 41: 14885-14896Crossref PubMed Scopus (286) Google Scholar)). On the other hand, tau has a hydrophilic character, is highly soluble, and belongs to the class of natively unfolded proteins with no apparent ordered secondary structure detectable by far-UV CD or Fourier-transform infrared spect
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“Hexapeptide VQIINK motifs in the second repeat and VQIVYK in the third repeat within the tau microtubule-binding domain are crucial for the formation of β-sheet structures and consequent tau aggregation [221, 222].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [221]
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“These good correlations between the REMD- and NMR-derived Cα chemical shifts indicate that the REMD-generated conformational ensemble of K18 monomer is consistent with previous NMR data.371”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [371]
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“The REMD-predicted and experimentally measured Cα SCSs show a Pearson correlation coefficient of 0.614 (Fig. 6 C), consistent with previous NMR data.371”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [371]
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“Protein-protein interfaces are characterized by the existence of hot spots or ‘hot regions’ in interacting regions instead of an even contribution across all contact areas.371,476,487,492–495”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [371]
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Cites
NMRPipe: A multidimensional spectral processing system based on UNIX pipes
Delaglio, F., Grzesiek, S., Vuister, G. W., Zhu, G., Pfeifer, J., & Bax, A. (1995) · Journal of Biomolecular NMR · doi:10.1007/bf00197809 · Cited by 15,961
Why are ?natively unfolded? proteins unstructured under physiologic conditions?
Uversky, V. N., Gillespie, J. R., & Fink, A. L. (2000) · Proteins Structure Function and Bioinformatics · doi:10.1002/1097-0134(20001115)41:3 · Cited by 2,097
Goedert, M., Jakes, R., Spillantini, M. G., Hasegawa, M., Smith, M. J., & Crowther, R. A. (1996) · Nature · doi:10.1038/383550a0 · Cited by 1,036
Mandelkow, E. (1998) · Trends in Cell Biology · doi:10.1016/s0962-8924(98)01368-3 · Cited by 980
Self-citationWischik, C. M., Novak, M., Thøgersen, H. C., Edwards, P. C., Runswick, M. J., Jakes, R., Walker, J. E., Milstein, C., Roth, M., & Klug, A. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.12.4506 · Cited by 939
[12] Chemical shifts as a tool for structure determination
Wishart, D. S., & Sykes, B. D. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(94)39014-2 · Cited by 874
Alzheimer's Disease: Molecular Understanding Predicts Amyloid-Based Therapeutics
Selkoe, D. J., & Schenk, D. (2003) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.43.100901.140248 · Cited by 829
Bertoncini, C. W., Jung, Y., Fernández, C. O., Hoyer, W., Griesinger, C., Jovin, T. M., & Zweckstetter, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407146102 · Cited by 802
Self-citationBiernat, J., Gustke, N., Drewes, G., Mandelkow, E., & Mandelkow, E. (1993) · Neuron · doi:10.1016/0896-6273(93)90279-z · Cited by 796
Self-citationMethodological advances in protein NMR
Bax, A., & Grzesiek, S. (1993) · Accounts of Chemical Research · doi:10.1021/ar00028a001 · Cited by 775
Flagged first, then by citations
Research works printed but not linked: 2
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- Craik, 1997, Methods Mol. Biol., 60, 195
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Mandelkow, E., & Mandelkow, E. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006247 · Cited by 897
Self-citationAmbadipudi, S., Biernat, J., Riedel, D., Mandelkow, E., & Zweckstetter, M. (2017) · Nature Communications · doi:10.1038/s41467-017-00480-0 · Cited by 782
Self-citationThe acetylation of tau inhibits its function and promotes pathological tau aggregation
Cohen, T. J., Guo, J. L., Hurtado, D. E., Kwong, L. K., Mills, I. P., Trojanowski, J. Q., & Lee, V. M. Y. (2011) · Nature Communications · doi:10.1038/ncomms1255 · Cited by 724
Nguyen, P. H., Ramamoorthy, A., Sahoo, B. R., Zheng, J., Faller, P., Straub, J. E., Domínguez, L., Shea, J., Dokholyan, N. V., Simone, A. D., et al. (2021) · Chemical Reviews · doi:10.1021/acs.chemrev.0c01122 · Cited by 680
Structural Polymorphism of 441-Residue Tau at Single Residue Resolution
Mukrasch, M. D., Bibow, S., Korukottu, J., Jeganathan, S., Biernat, J., Griesinger, C., Mandelkow, E., & Zweckstetter, M. (2009) · PLoS Biology · doi:10.1371/journal.pbio.1000034 · Cited by 652
Self-citationArendt, T., Stieler, J. T., & Holzer, M. (2016) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2016.08.018 · Cited by 609
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Wei, G., Xi, W., Nussinov, R., & Ma, B. (2016) · Chemical Reviews · doi:10.1021/acs.chemrev.5b00562 · Cited by 436
Proteases and Proteolysis in Alzheimer Disease: A Multifactorial View on the Disease Process
De Strooper, B. (2010) · Physiological Reviews · doi:10.1152/physrev.00023.2009 · Cited by 455
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Naseri, N. N., Wang, H., Guo, J. D., Sharma, M., & Luo, W. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.04.022 · Cited by 393
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Khlistunova, I., Biernat, J., Wang, Y., Pickhardt, M., von Bergen�, M., Gažová, Z., Mandelkow�, E., & Mandelkow, E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m507753200 · Cited by 366
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Mukrasch, M. D., Markwick, P. R. L., Biernat, J., von Bergen�, M., Bernadó, P., Griesinger, C., Mandelkow�, E., Zweckstetter, M., & Blackledge, M. J. (2007) · Journal of the American Chemical Society · doi:10.1021/ja0690159 · Cited by 222
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Self-citationUpdates in Alzheimer's disease: from basic research to diagnosis and therapies
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Andronesi, O. C., Bergen, M. V., Biernat, J., Seidel, K., Griesinger, C., Mandelkow, E., & Baldus, M. (2008) · Journal of the American Chemical Society · doi:10.1021/ja7100517 · Cited by 167
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Self-citationFischer, D., Mukrasch, M. D., Biernat, J., Bibow, S., Blackledge, M., Griesinger, C., Mandelkow, E., & Zweckstetter, M. (2009) · Biochemistry · doi:10.1021/bi901090m · Cited by 149
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Self-citationvon Bergen�, M., Barghorn, S., Müller, S. A., Pickhardt, M., Biernat, J., Mandelkow, E., Davies, P., Aebi, U., & Mandelkow�, E. (2006) · Biochemistry · doi:10.1021/bi052530j · Cited by 141
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Gallat, F., Laganowsky, A. D., Wood, K., Gabel, F., van Eijck, L., Wuttke, J., Moulin, M., Haertlein, M., Eisenberg, D. S., Colletier, J., et al. (2012) · Biophysical Journal · doi:10.1016/j.bpj.2012.05.027 · Cited by 103
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Sarkar, M., Kuret, J., & Lee, G. S. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21721 · Cited by 96
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Self-citationWang, X., Dong, C., Zhang, J., Wan, Y.-Z., Li, F., Huang, Y.-X., Han, L., Shan, B., Gao, C., Han, J., et al. (2007) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-007-9664-6 · Cited by 75
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Metadata
- Authors
- Mukrasch, M. D., Biernat, J., von Bergen, M., Griesinger, C., Mandelkow, E., & Zweckstetter, M.
- Affiliations
- Max Planck Institute for Biophysical Chemistry (DE)
- Deutsches Elektronen-Synchrotron DESY (DE)
- Corresponding author
- Zweckstetter, Markus
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 280
- Issue
- 26
- Pages
- 24978-24986
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2079615523
- Cited by
- 324
- References
- 39
- Citations by year
- 2026: 11 · 2025: 19 · 2024: 10 · 2023: 18 · 2022: 20 · 2021: 21 · 2020: 23 · 2019: 24 · 2018: 21 · 2017: 11 · 2016: 17 · 2015: 13 · 2014: 13 · 2013: 16 · 2012: 17
- FWCI
- 8.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Max Planck Institute for Plasma Physics (submittedVersion)
- GRO (submittedVersion)
- Funders
- European Commission
- Deutsche Forschungsgemeinschaft
- Max-Planck-Gesellschaft
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- tau protein, protein aggregation, neurofibrillary tangles, Alzheimer's disease, microtubule binding, polyanion binding, paired helical filaments, cross-β structure, tau repeat domain, secondary structure, chemical shift perturbation, protein-protein interaction sites, intrinsically disordered proteins, microtubule stabilization, chemical shift assignment
- MeSH terms
- Polyelectrolytes, Alzheimer Disease, Amino Acid Sequence, Animals, Anions, Brain, Electrophoresis, Polyacrylamide Gel, Humans, Lysine, Microtubules, Molecular Sequence Data, Mutation, Magnetic Resonance Spectroscopy, Polymers, Protein Binding, Swine, Temperature, Tubulin, Neurofibrillary Tangles, tau Proteins, Sequence Homology, Amino Acid, Protein Structure, Secondary, Protein Structure, Tertiary, Protein Folding, Crystallography, X-Ray, Protein Isoforms
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