ArticleeLife2015
Sampling the conformational space of the catalytic subunit of human γ-secretase.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 354 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
354 citing papers in PubMed, 598 citations in OpenAlex.
- The γ-secretase complex: from discovery to a therapeutic target.RSC chemical biology · 2026Review
- Conformational Flexibility of Transmembrane Helices: How it Works and Where it Matters.Chemical reviews · 2026Review
- Structural insights into the activation of the chicken ROS1 receptor by the NEL/NICOL ligand complex.Nature communications · 2026Article
- Molecular basis of XPF-ERCC1 targeting to SLX4-dependent DNA repair pathways.Nature communications · 2025Article
- Mechanism for the substrate recognition by a eukaryotic DNA NNature communications · 2025Article
- Economical and Versatile Subunit Design Principles for Self-Assembled DNA Origami Structures.ACS nano · 2025Article
- Cryo-EM structure of ribosome from pathogenic protozoa Entamoeba histolytica reveals unique features of its architecture.Nature communications · 2025Article
- A common structural mechanism for RNA recognition by the SF3B complex in mRNA splicing and export.Nucleic acids research · 2025Article
- The mechanism for GTP-mediated RNA capping by the SARS-CoV-2 NiRAN domain remains unresolved.Cell · 2025Article
- Mechanism of human α3β GlyR regulation by intracellular M3/M4 loop phosphorylation and 2,6-di-tert-butylphenol interaction.Nature communications · 2025Article
- Structural insights into the ubiquitin-independent midnolin-proteasome pathway.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Maintaining the Integral Membrane Proteome: Revisiting the Functional Repertoire of Integral Membrane Proteases.Chembiochem : a European journal of chemical biology · 2025Review
- CryoEM and crystal structure analyses reveal the indirect role played by Trp89 in glutamate dehydrogenase enzymatic reactions.The FEBS journal · 2025Article
- A tRNA modification with aminovaleramide facilitates AUA decoding in protein synthesis.Nature chemical biology · 2025Article
- The membrane-proximal external region of human immunodeficiency virus (HIV-1) envelope glycoprotein trimers in A18-lipid nanodiscs.Communications biology · 2025Article
- Comprehensive investigation of multiple targets in the development of newer drugs for the Alzheimer's disease.Acta pharmaceutica Sinica. B · 2025Review
- In situ and in vitro cryo-EM reveal structures of mycobacterial encapsulin assembly intermediates.Communications biology · 2025Article
- A distinct double-ring LH1-LH2 photocomplex from an extremophilic phototroph.Nature communications · 2025Article
- Multi-target-directed therapeutic strategies for Alzheimer's disease: controlling amyloid-β aggregation, metal ion homeostasis, and enzyme inhibition.Chemical science · 2025Review
- A Native LH1-RC-HiPIP Supercomplex from an Extremophilic Phototroph.Communications biology · 2025Article
294 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Human γ-secretase is an intra-membrane protease that cleaves many different substrates. Aberrant cleavage of Notch is implicated in cancer, while abnormalities in cutting amyloid precursor protein lead to Alzheimer's disease. Our previous cryo-EM structure of γ-secretase revealed considerable disorder in its catalytic subunit presenilin. Here, we describe an image classification procedure that characterizes molecular plasticity at the secondary structure level, and apply this method to identify three distinct conformations in our previous sample. In one of these conformations, an additional transmembrane helix is visible that cannot be attributed to the known components of γ-secretase. In addition, we present a γ-secretase structure in complex with the dipeptidic inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT). Our results reveal how conformational mobility in the second and sixth transmembrane helices of presenilin is greatly reduced upon binding of DAPT or the additional helix, and form the basis for a new model of how substrate enters the transmembrane domain.
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Registered trials
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.