Molecular dynamics simulation of the SH3 domain aggregation suggests a generic amyloidogenesis mechanism.

@article{Ding2002MolecularDS,
  title={Molecular dynamics simulation of the SH3 domain aggregation suggests a generic amyloidogenesis mechanism.},
  author={Feng Ding and Nikolay V. Dokholyan and Sergey V. Buldyrev and Harry Eugene Stanley and Eugene I. Shakhnovich},
  journal={Journal of molecular biology},
  year={2002},
  volume={324 4},
  pages={
          851-7
        }
}

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References

SHOWING 1-10 OF 41 REFERENCES

A proposed structural model for amyloid fibril elongation: domain swapping forms an interdigitating beta-structure polymer.

A model illustrating how proteins, which differ in their overall sequences and structures, can form the propagating, twisted beta-sheet conformations, characteristic of amyloids, shows how the swapping of beta-hairpins would form an interdigitated, twistedbeta-sheet conformation, explaining the remarkable high stability of the protofibril in vitro.

A domain-swapped RNase A dimer with implications for amyloid formation

The hinge loop of the major dimer, connecting the swapped β-strand to the protein core, resembles a short segment of the polar zipper proposed by Perutz and suggests a model for aggregate formation by 3D domain swapping with a polar zipper.

Mechanisms of cooperativity underlying sequence-independent β-sheet formation

The results suggest that solvation dynamics together with the H-bond angular dependence gives rise to a generic cooperativity in this class of systems; this result explains why pathological aggregates involving β-sheet cores can form from many different proteins.

Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping

The crystal structure of human cystatin C, a protein with amyloidogenic properties and a potent inhibitor of cysteine proteases, reveals how the protein refolds to produce very tight two-fold

Amyloid fibril formation by an SH3 domain.

Results indicate that the A state of PI3-SH3 is partially folded and support the hypothesis that partially folded states formed in solution are precursors of amyloid deposition.

Important role of hydrogen bonds in the structurally polarized transition state for folding of the src SH3 domain

A hydrogen bond network involving two β-turns and an adjacent hydrophobic cluster appear to be formed in the folding transition state of the src SH3 domain, while the remainder of the polypeptide chain is largely unstructured.

Three‐dimensional domain swapping in the folded and molten‐globule states of cystatins, an amyloid‐forming structural superfamily

Dimmerization also occurs when chicken cystatin is in its reduced, molten‐globule state, implying that the organization of secondary structure in this state mirrors that in the folded state and that domain swapping is not limited to the folded states of proteins.

Domain swapping: entangling alliances between proteins.

Several other intertwined, dimeric protein structures satisfy the definition of domain swapping and suggest that domain swapping may be the molecular mechanism for evolution of these oligomers and possibly of oligomeric proteins in general.

The alternative conformations of amyloidogenic proteins and their multi-step assembly pathways.

  • J. Kelly
  • Biology, Chemistry
    Current opinion in structural biology
  • 1998