The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
The E46K Mutation in α-Synuclein Increases Amyloid Fibril Formation
Open accessAbstract
The identification of a novel mutation (E46K) in one of the KTKEGV-type repeats in the amino-terminal region of alpha-synuclein suggests that this region and, more specifically, Glu residues in the repeats may be important in regulating the ability of alpha-synuclein to polymerize into amyloid fibrils. It was demonstrated that the E46K mutation increased the propensity of alpha-synuclein to fibrillize, but this effect was less than that of the A53T mutation. The substitution of Glu(46) for an Ala also increased the assembly of alpha-synuclein, but the polymers formed can have different ultrastructures, further indicating that this amino acid position has a significant effect on the assembly process. The effect of residue Glu(83) in the sixth repeat of alpha-synuclein, which lies closest to the amino acid stretch critical for filament assembly, was also studied. Mutation of Glu(83) to a Lys or Ala increased polymerization but perturbed some of the properties of mature amyloid. These results demonstrated that some of the Glu residues within the repeats can have significant effects on modulating the assembly of alpha-synuclein to form amyloid fibrils. The greater effect of the A53T mutation, even when compared with what may be predicted to be a more dramatic mutation such as E46K, underscores the importance of protein microenvironment in affecting protein structure. Moreover, the relative effects of the A53T and E46K mutations are consistent with the age of onset of disease. These findings support the notion that aberrant alpha-synuclein polymerization resulting in the formation of pathological inclusions can lead to disease.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Spillantini, M. G., Schmidt, M. L., Lee, V. M.-Y., Trojanowski, J. Q., Jakes, R., & Goedert, M. (1997) · Nature · doi:10.1038/42166 · Cited by 8,382
Mutation in the α-Synuclein Gene Identified in Families with Parkinson's Disease
Polymeropoulos, M. H., Lavedan, C., Leroy, E., Ide, S. E., Dehejia, A., Dutra, A., Pike, B., Root, H., Rubenstein, J., Boyer, R., et al. (1997) · Science · doi:10.1126/science.276.5321.2045 · Cited by 8,240
AlaSOPro mutation in the gene encoding α-synuclein in Parkinson's disease
Krüger, R., Kuhn, W., Müller, T., Woitalla, D., Graeber, M., Kösel, S., Przuntek, H., Epplen, J. T., Schols, L., & Riess, O. (1998) · Nature Genetics · doi:10.1038/ng0298-106 · Cited by 3,836
Prediction of protein conformation
Chou, P. Y., & Fasman, G. D. (1974) · Biochemistry · doi:10.1021/bi00699a002 · Cited by 3,309
Chou, P. Y., & Fasman, G. D. (1974) · Biochemistry · doi:10.1021/bi00699a001 · Cited by 2,172
Mice Lacking α-Synuclein Display Functional Deficits in the Nigrostriatal Dopamine System
Abeliovich, A., Schmitz, Y., Fariñas, I., Choi-Lundberg, D., Ho, W.-H., Castillo, P. E., Shinsky, N., Verdugo, J. M. G., Armanini, M., Ryan, A., et al. (2000) · Neuron · doi:10.1016/s0896-6273(00)80886-7 · Cited by 1,722
Iwai, A., Masliah, E., Yoshimoto, M., Ge, N., Flanagan, L., Rohan de Silva, H. A., Kittel, A., & Saitoh, T. (1995) · Neuron · doi:10.1016/0896-6273(95)90302-x · Cited by 1,316
Evidence for a Partially Folded Intermediate in α-Synuclein Fibril Formation
Uversky, V. N., Li, J., & Fink, A. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m010907200 · Cited by 1,096
Giasson, B. I., Murray, I. V. J., Trojanowski, J. Q., & Lee, V. M.-Y. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008919200 · Cited by 1,080
Self-citationTu, P., Galvin, J. E., Baba, M., Giasson, B., Tomita, T., Leight, S., Nakajo, S., Iwatsubo, T., Trojanowski, J. Q., & Lee, V. M. ‐. (1998) · Annals of Neurology · doi:10.1002/ana.410440324 · Cited by 686
Self-citation
Cited by
α‐Synuclein aggregation nucleates through liquid‐liquid phase separation
Ray, S., Singh, N., Kumar, R., Patel, K., Pandey, S., Datta, D., Mahato, J., Panigrahi, R., Navalkar, A., Mehra, S., et al. (2020) · Nature Chemistry · doi:10.1038/s41557-020-0465-9 · Cited by 863
A century-old debate on protein aggregation and neurodegeneration enters the clinic
Lansbury, P. T., & Lashuel, H. A. (2006) · Nature · doi:10.1038/nature05290 · Cited by 687
Distinct α-Synuclein Strains Differentially Promote Tau Inclusions in Neurons
Guo, J. L., Covell, D. J., Daniels, J. P., Iba, M., Stieber, A., Zhang, B., Riddle, D. M., Kwong, L. K., Xu, Y., Trojanowski, J. Q., et al. (2013) · Cell · doi:10.1016/j.cell.2013.05.057 · Cited by 680
α-Synuclein misfolding and Parkinson's disease
Breydo, L., Wu, J. W., & Uversky, V. N. (2012) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2011.10.002 · Cited by 657
Cell Biology and Pathophysiology of α-Synuclein
Burré, J., Sharma, M., & Südhof, T. C. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024091 · Cited by 579
Metadata
- Authors
- Greenbaum, E. A., Graves, C. L., Mishizen-Eberz, A. J., Lupoli, M. A., Lynch, D. R., Englander, S. W., Axelsen, P. H., & Giasson, B. I.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-03
- Volume
- 280
- Issue
- 9
- Pages
- 7800-7807
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2144435948
- Cited by
- 370
- References
- 11
- FWCI
- 15.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: The E46K Mutation in α-Synuclein Increases Amyloid Fibril Formation. https://app.cochat.ai/papers/10.1074/jbc.m411638200
- The paper
- Greenbaum, E. A., Graves, C. L., Mishizen-Eberz, A. J., Lupoli, M. A., Lynch, D. R., Englander, S. W., Axelsen, P. H., & Giasson, B. I. (2005). The E46K Mutation in α-Synuclein Increases Amyloid Fibril Formation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m411638200
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
