Putative aggregation initiation sites in prion protein

@article{Ziegler2006PutativeAI,
  title={Putative aggregation initiation sites in prion protein},
  author={Jan Ziegler and Christine Viehrig and Stefan Geimer and Paul Rösch and Stephan Schwarzinger},
  journal={FEBS Letters},
  year={2006},
  volume={580}
}
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29 Citations
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29 Citations

Spontaneous β‐helical fold in prion protein: The case of PrP(82‐146)
TLDR
Structural features of the observed 82‐146 β‐helical fold are compatible with the “dock and lock” mechanism proposed to interpret peptide aggregation kinetics.
The protonation state of histidine 111 regulates the aggregation of the evolutionary most conserved region of the human prion protein
TLDR
The study highlights the importance of protonation of histidine residues for protein aggregation and suggests point mutations to probe the structure of infectious prion particles.
Structural and hydration properties of the partially unfolded states of the prion protein.
TLDR
The free energy surface of the C-terminal globular domain of the PrP is constructed from enhanced sampling of replica exchange molecular dynamics to gain insights into possible aggregation-prone intermediate states.
The intrinsic stability of the human prion β-sheet region investigated by molecular dynamics
TLDR
The extensive sampling of replica exchange shows that the native antiparallel β-structure of the prion is endowed with a remarkable stability, and upon unfolding, the persistence of a structured β-region may seed molecular association and influence the subsequent phases of the aggregation process.
Unraveling the Histidine Tautomerism Effect on the Initial Stages of Prion Misfolding: New Insights from a Computational Perspective.
TLDR
The histidine tautomerization hypothesis is proposed as a new prion accumulation mechanism, which may exist to induce the formation of prion accumulates and may help in the design of a good inhibitor.
Rare Large Scale Subdomain Motions in Stephan Schwarzinger17* Prion Protein can Initiate Aggregation Anseh H. C. Horn2
TLDR
It is proposed that a novel concept that involves rare large scale motions between the subdomains s1-al-s2 and a2-a3 in the carboxy-terminal, globular part of PrP contributes to the formation of pathogenic oligomeric species of the prion protein.
Pathogenic Mutations within the Disordered Palindromic Region of the Prion Protein Induce Structure Therein and Accelerate the Formation of Misfolded Oligomers
TLDR
Kinetic hydrogen–deuterium exchange–mass spectrometry experiments show that sequence segment 89–132 from the NTR becomes structured, albeit weakly, during the oligomerization of both mutant variants, and appears to be the reason that the formation of misfolded oligomers is accelerated by the pathogenic mutations.
Pathogenic Mutations within the Disordered Palindromic Region of the Prion Protein Induce Structure Therein and Accelerate the Formation of Misfolded Oligomers.
Copper Alters Aggregation Behavior of Prion Protein and Induces Novel Interactions between Its N- and C-terminal Regions
TLDR
This study investigates the conformational consequences of Cu2+-binding to full-length prion protein (PrP) by isothermal calorimetry, NMR, and small angle x-ray scattering and demonstrates novel long range inter-domain interactions of the N- and C-terminal regions of PrP upon Cu2+.
Prion protein self-peptides modulate prion interactions and conversion
TLDR
This study identified the putative PrP core binding domain that facilitates the PrPC-PrPSc interaction (not conversion), corroborating evidence that the region of PrP containing this domain is important in the species-barrier and/or scrapie susceptibility.
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References

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Propagation of transmissible spongiform encephalopathies is believed to involve the conversion of cellular prion protein, PrPC, into a misfolded oligomeric form, PrPSc. An important step toward…
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TLDR
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TLDR
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TLDR
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TLDR
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TLDR
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Most of the structural elements of the globular domain of murine prion protein form fibrils with predominant β‐sheet structure
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