ArticleJournal of molecular biology2011
Molecular determinants and thermodynamics of the amyloid precursor protein transmembrane domain implicated in Alzheimer's disease.
Article in Journal of molecular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- High-throughput discovery of transmembrane helix dimers from human single-pass membrane proteins with TOXGREEN sort-seq.PNAS nexus · 2025Article
- Effect of Cholesterol on C99 Dimerization: Revealed by Molecular Dynamics Simulations.Frontiers in molecular biosciences · 2022Article
- Bicelles Rich in both Sphingolipids and Cholesterol and Their Use in Studies of Membrane Proteins.Journal of the American Chemical Society · 2020Article
- De novo aggregation of Alzheimer's Aβ25-35 peptides in a lipid bilayer.Scientific reports · 2019Article
- Coupled Transmembrane Substrate Docking and Helical Unwinding in Intramembrane Proteolysis of Amyloid Precursor Protein.Scientific reports · 2018Article
- Dissecting conformational changes in APP's transmembrane domain linked to ε-efficiency in familial Alzheimer's disease.PloS one · 2018Article
- Dimerization of the transmembrane domain of amyloid precursor protein is determined by residues around the γ-secretase cleavage sites.The Journal of biological chemistry · 2017Article
- Backbone Hydrogen Bond Strengths Can Vary Widely in Transmembrane Helices.Journal of the American Chemical Society · 2017Article
- Screening for transmembrane association in divisome proteins using TOXGREEN, a high-throughput variant of the TOXCAT assay.Biochimica et biophysica acta · 2016Article
- Impact of membrane lipid composition on the structure and stability of the transmembrane domain of amyloid precursor protein.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Extension of a protein docking algorithm to membranes and applications to amyloid precursor protein dimerization.Proteins · 2015Article
- Structural heterogeneity in transmembrane amyloid precursor protein homodimer is a consequence of environmental selection.Journal of the American Chemical Society · 2014Article
- Impact of bilayer lipid composition on the structure and topology of the transmembrane amyloid precursor C99 protein.Journal of the American Chemical Society · 2014Article
- Independent relationship between amyloid precursor protein (APP) dimerization and γ-secretase processivity.PloS one · 2014Article
- Familial Alzheimer's mutations within APPTM increase Aβ42 production by enhancing accessibility of ε-cleavage site.Nature communications · 2014Article
- Cholesterol as a co-solvent and a ligand for membrane proteins.Protein science : a publication of the Protein Society · 2014Review
- Competition between homodimerization and cholesterol binding to the C99 domain of the amyloid precursor protein.Biochemistry · 2013Article
- The backbone dynamics of the amyloid precursor protein transmembrane helix provides a rationale for the sequential cleavage mechanism of γ-secretase.Journal of the American Chemical Society · 2013Article
- A transmembrane domain and GxxxG motifs within L2 are essential for papillomavirus infection.Journal of virology · 2013Article
- Modulation of γ-secretase activity by multiple enzyme-substrate interactions: implications in pathogenesis of Alzheimer's disease.PloS one · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The deposition of toxic amyloid-β (Aβ) peptide aggregates in the brain is a hallmark of Alzheimer's disease. The intramembrane proteolysis by γ-secretase of the amyloid precursor protein β-carboxy-terminal fragment (APP-βCTF) constitutes the final step in the production of Aβ peptides. Mounting evidence suggests that APP-βCTF is a transmembrane domain (TMD) dimer, and that dimerization might modulate the production of Aβ species that are prone to aggregation and are therefore most toxic. We combined experimental and computational approaches to study the molecular determinants and thermodynamics of APP-βCTF dimerization, and we produced a unifying structural model that reconciles much of the published data. Using a cell assay that exploits a dimerization-dependent activator of transcription, we identified specific dimerization-affecting mutations located mostly at the N-terminus of the TMD of APP-βCTF. The ability of selected mutants to affect the dimerization of full-length APP-βCTF was confirmed by fluorescence resonance energy transfer experiments. Free-energy estimates of the wild type and mutants of the TMD of APP-βCTF derived from enhanced molecular dynamics simulations showed that the dimeric state is composed of different arrangements, in which either (709)GXXXA(713) or (700)GXXXG(704)GXXXG(708) interaction motifs can engage in symmetric or asymmetric associations. Mutations along the TMD of APP-βCTF were found to modulate the relative free energy of the dimeric configurations and to differently affect the distribution of interfaces within the dimeric state. This observation might have important biological implications, since dimers with a different arrangement of the transmembrane helices are likely to be recognized differently by γ-secretase and to lead to a variation in Aβ levels.
Indexed as
Identifiers
What OpenQuestion holds
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.