The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
An atomic structure of human γ-secretase
Open accessAbstract
Dysfunction of the intramembrane protease γ-secretase is thought to cause Alzheimer’s disease, with most mutations derived from Alzheimer’s disease mapping to the catalytic subunit presenilin 1 (PS1). Here we report an atomic structure of human γ-secretase at 3.4 Å resolution, determined by single-particle cryo-electron microscopy. Mutations derived from Alzheimer’s disease affect residues at two hotspots in PS1, each located at the centre of a distinct four transmembrane segment (TM) bundle. TM2 and, to a lesser extent, TM6 exhibit considerable flexibility, yielding a plastic active site and adaptable surrounding elements. The active site of PS1 is accessible from the convex side of the TM horseshoe, suggesting considerable conformational changes in nicastrin extracellular domain after substrate recruitment. Component protein APH-1 serves as a scaffold, anchoring the lone transmembrane helix from nicastrin and supporting the flexible conformation of PS1. Ordered phospholipids stabilize the complex inside the membrane. Our structure serves as a molecular basis for mechanistic understanding of γ-secretase function.
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Cites
Coot : model-building tools for molecular graphics
Emsley, P., & Cowtan, K. (2004) · Acta Crystallographica Section D Biological Crystallography · doi:10.1107/s0907444904019158 · Cited by 30,571
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Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484
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De Strooper, B. (2014) · Cell · doi:10.1016/j.cell.2014.10.016 · Cited by 277
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De Strooper, B., & Karran, E. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00057-w · Cited by 36
Spitz, C., Schlosser, C., Guschtschin-Schmidt, N., Stelzer, W., Menig, S., Götz, A., Haug-Kröper, M., Scharnagl, C., Langosch, D., Muhle-Goll, C., et al. (2020) · iScience · doi:10.1016/j.isci.2020.101775 · Cited by 23
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Metadata
- Authors
- Bai, X.-C., Yan, C., Yang, G., Lu, P., Ma, D., Sun, L., Zhou, R., Scheres, S. H. W., & Shi, Y.
- Venue
- Nature
- Published
- 2015-08-17
- Volume
- 525
- Issue
- 7568
- Pages
- 212-217
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1890431460
- Cited by
- 498
- References
- 3
- FWCI
- 48.85
- Type
- journal article
- Language
- en
- Open access
- green
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