The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Three-dimensional structure of human γ-secretase
Open accessAbstract
The γ-secretase complex, comprising presenilin 1 (PS1), PEN-2, APH-1 and nicastrin, is a membrane-embedded protease that controls a number of important cellular functions through substrate cleavage. Aberrant cleavage of the amyloid precursor protein (APP) results in aggregation of amyloid-β, which accumulates in the brain and consequently causes Alzheimer’s disease. Here we report the three-dimensional structure of an intact human γ-secretase complex at 4.5 Å resolution, determined by cryo-electron-microscopy single-particle analysis. The γ-secretase complex comprises a horseshoe-shaped transmembrane domain, which contains 19 transmembrane segments (TMs), and a large extracellular domain (ECD) from nicastrin, which sits immediately above the hollow space formed by the TM horseshoe. Intriguingly, nicastrin ECD is structurally similar to a large family of peptidases exemplified by the glutamate carboxypeptidase PSMA. This structure serves as an important basis for understanding the functional mechanisms of the γ-secretase complex.
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Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein
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Aph-1, Pen-2, and Nicastrin with Presenilin Generate an Active γ-Secretase Complex
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Cited by
Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development
Chen, G.-F., Xu, T.-H., Yan, Y., Zhou, Y.-R., Jiang, Y., Melcher, K., & Xu, H. E. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.28 · Cited by 1,965
EMRinger: side chain–directed model and map validation for 3D cryo-electron microscopy
Barad, B. A., Echols, N., Wang, R. Y.-R., Cheng, Y., DiMaio, F., Adams, P. D., & Fraser, J. S. (2015) · Nature Methods · doi:10.1038/nmeth.3541 · Cited by 886
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0063-8 · Cited by 723
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Self-citationRecognition of the amyloid precursor protein by human γ-secretase
Zhou, R., Yang, G., Guo, X., Zhou, Q., Lei, J., & Shi, Y. (2019) · Science · doi:10.1126/science.aaw0930 · Cited by 304
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Metadata
- Authors
- Lu, P., Bai, X.-C., Ma, D., Xie, T., Yan, C., Sun, L., Yang, G., Zhao, Y., Zhou, R., Scheres, S. H. W., & Shi, Y.
- Venue
- Nature
- Published
- 2014-06-29
- Volume
- 512
- Issue
- 7513
- Pages
- 166-170
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1552188451
- Cited by
- 346
- References
- 5
- FWCI
- 32.07
- Type
- journal article
- Language
- en
- Open access
- green
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- Lu, P., Bai, X.-C., Ma, D., Xie, T., Yan, C., Sun, L., Yang, G., Zhao, Y., Zhou, R., Scheres, S. H. W., & Shi, Y. (2014). Three-dimensional structure of human γ-secretase. Nature. https://doi.org/10.1038/nature13567
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