ArticleBiophysical journal2008
Modeling by assembly and molecular dynamics simulations of the low Cu2+ occupancy form of the mammalian prion protein octarepeat region: gaining insight into Cu2+-mediated beta-cleavage.
Article in Biophysical journal, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 23 citations in OpenAlex.
- Application of N-Terminal Labeling Methods Provide Novel Insights into Endoproteolysis of the Prion ProteinACS chemical neuroscience · 2024Article
- Prion Protein Octarepeat Domain Forms Transient β-Sheet Structures upon Residue-Specific Binding to Cu(II) and Zn(II) Ions.Biochemistry · 2023Article
- Prion Protein: The Molecule of Many Forms and Faces.International journal of molecular sciences · 2022Review
- Both N-Terminal and C-Terminal Histidine Residues of the Prion Protein Are Essential for Copper Coordination and Neuroprotective Self-Regulation.Journal of molecular biology · 2020Article
- Altered Domain Structure of the Prion Protein Caused by CuStructure (London, England : 1993) · 2019Article
- Substitutions of PrP N-terminal histidine residues modulate scrapie disease pathogenesis and incubation time in transgenic mice.PloS one · 2017Article
- Interaction between Prion Protein's Copper-Bound Octarepeat Domain and a Charged C-Terminal Pocket Suggests a Mechanism for N-Terminal Regulation.Structure (London, England : 1993) · 2016Article
- Octarepeat region flexibility impacts prion function, endoproteolysis and disease manifestation.EMBO molecular medicine · 2015Article
- Combined EXAFS and DFT structure calculations provide structural insights into the 1:1 multi-histidine complexes of Cu(II) , Cu(I) , and Zn(II) with the tandem octarepeats of the mammalian prion protein.Chemistry (Weinheim an der Bergstrasse, Germany) · 2014Article
- Copper-induced structural propensities of the amyloidogenic region of human prion protein.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2014Article
- New insights into metal interactions with the prion protein: EXAFS analysis and structure calculations of copper binding to a single octarepeat from the prion protein.The journal of physical chemistry. B · 2013Article
- Proteolytic processing of the prion protein in health and disease.American journal of neurodegenerative disease · 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
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The prion protein has garnered considerable interest because of its involvement in prion disease as well as its unresolved cellular function. The octarepeat region in the flexible N-domain is capable of binding copper through multiple coordination modes. Under conditions of low pH and low Cu(2+) concentration, the four octarepeats (ORs) cooperatively coordinate a single copper ion. Based on the average structure of the PHGG and GWGQ portions of a copper-free OR(2) model from molecular dynamics simulations, the starting structures of the OR(4) complex could be constructed by assembling the repeating structure of PHGG and GWGQ fragments. The resulting model contains a preformed site suitable for Cu(2+) coordination. Molecular dynamics simulations of Cu(2+) bound to the assembled OR(4) model (Cu:OR(4)) reveal a close association of specific Trp and Gly residues with the Cu(2+) center. This low Cu(2+)-occupancy form of prion protein is redox-active and can readily initiate cleavage of the OR region, mediated by reactive oxygen species generated by Cu(+). The OR region is known to be required for beta-cleavage, as are the Trp residues within the OR region. The beta-cleaved form of the prion protein accumulates in amyloid fibrils. Hence, the close approach of Trp and Gly residues to the Cu(2+) coordination site in the low Cu(2+)-occupancy form of the OR region may signal an important interaction for the initiation of prion disease.
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.