ArticleProceedings of the National Academy of Sciences of the United States of America2014
Crystal structure of the γ-secretase component nicastrin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 69 citations in OpenAlex.
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- Thermal proteome profiling unveils protein targets of deoxycholic acid in living neuronal cells.Advanced biotechnology · 2023Article
- γ-secretase promotes Drosophila postsynaptic development through the cleavage of a Wnt receptor.Developmental cell · 2022Article
- Interpreting the spectrum of gamma-secretase complex missense variation in the context of hidradenitis suppurativa-AnFrontiers in genetics · 2022Article
- The Genomic Architecture of Hidradenitis Suppurativa-A Systematic Review.Frontiers in genetics · 2022Review
- Fosciclopirox suppresses growth of high-grade urothelial cancer by targeting the γ-secretase complex.Cell death & disease · 2021Article
- Celastrol and Triptolide Suppress Stemness in Triple Negative Breast Cancer: Notch as a Therapeutic Target for Stem Cells.Biomedicines · 2021Article
- The dark side of Alzheimer's disease: unstructured biology of proteins from the amyloid cascade signaling pathway.Cellular and molecular life sciences : CMLS · 2020Article
- Integrated structural and evolutionary analysis reveals common mechanisms underlying adaptive evolution in mammals.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Substrate-Enzyme Interactions in Intramembrane Proteolysis: γ-Secretase as the Prototype.Frontiers in molecular neuroscience · 2020Review
- Structure and Function of the γ-Secretase Complex.Biochemistry · 2019Article
- Review
- Fighting the Cause of Alzheimer's and GNE Myopathy.Frontiers in neuroscience · 2018Review
- Allosteric Modulation of Intact γ-Secretase Structural Dynamics.Biophysical journal · 2017Article
- Structural and Chemical Biology of Presenilin Complexes.Cold Spring Harbor perspectives in medicine · 2017Review
- Characterizing the structural ensemble of γ-secretase using a multiscale molecular dynamics approach.Chemical science · 2017Article
- High-efficient production and biophysical characterisation of nicastrin and its interaction with APPC100.Scientific reports · 2017Article
- Evidence That the "Lid" Domain of Nicastrin Is Not Essential for Regulating γ-Secretase Activity.The Journal of biological chemistry · 2016Article
- Nicastrin functions to sterically hinder γ-secretase-substrate interactions driven by substrate transmembrane domain.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Structure of the transmembrane domain of human nicastrin-a component of γ-secretase.Scientific reports · 2016Article
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
γ-Secretase is an intramembrane protease responsible for the generation of amyloid-β (Aβ) peptides. Aberrant accumulation of Aβ leads to the formation of amyloid plaques in the brain of patients with Alzheimer's disease. Nicastrin is the putative substrate-recruiting component of the γ-secretase complex. No atomic-resolution structure had been identified on γ-secretase or any of its four components, hindering mechanistic understanding of γ-secretase function. Here we report the crystal structure of nicastrin from Dictyostelium purpureum at 1.95-Å resolution. The extracellular domain of nicastrin contains a large lobe and a small lobe. The large lobe of nicastrin, thought to be responsible for substrate recognition, associates with the small lobe through a hydrophobic pivot at the center. The putative substrate-binding pocket is shielded from the small lobe by a lid, which blocks substrate entry. These structural features suggest a working model of nicastrin function. Analysis of nicastrin structure provides insights into the assembly and architecture of the γ-secretase complex.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.