Structural properties of prion protein protofibrils and fibrils: an experimental assessment of atomic models.

Structural properties of prion protein protofibrils and fibrils: an experimental assessment of atomic models. Research Abstract Details 

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Structural properties of prion protein protofibrils and fibrils: an experimental assessment of atomic models. Abstract Text:

Mari L DeMarco,Jay Silveira,Byron Caughey,Valerie Daggett,Mari L DeMarco,Jay Silveira,Byron Caughey,Valerie Daggett,

Decades after the prion protein was implicated in transmissible spongiform encephalopathies, the structure of its toxic isoform and its mechanism of toxicity remain unknown. By gathering available experimental data, albeit low resolution, a few pieces of the prion puzzle can be put in place. Currently, there are two fundamentally different models of a prion protofibril. One has its building blocks derived from a molecular dynamics simulation of the prion protein under amyloidogenic conditions, termed the spiral model. The other model was constructed by threading a portion of the prion sequence through a beta-helical structure from the Protein Data Bank. Here we compare and contrast these models with respect to all of the available experimental information, including electron micrographs, symmetries, secondary structure, oligomerization interfaces, enzymatic digestion, epitope exposure, and disaggregation profiles. Much of this information was not available when the two models were introduced. Overall, we find that the spiral model is consistent with all of the experimental results. In contrast, it is difficult to reconcile several of the experimental observables with the beta-helix model. While the experimental constraints are of low resolution, in bringing together the previously disconnected experiments, we have developed a clearer picture of prion aggregates. Both the improved characterization of prion aggregates and the existing atomic models can be used to devise further experiments to better elucidate the misfolding pathway and the structure of prion protofibrils.

Structural properties of prion protein protofibrils and fibrils: an experimental assessment of atomic models. Publishing Authors By Initials

ML DeMarco,J Silveira,B Caughey,V Daggett,ML DeMarco,J Silveira,B Caughey,V Daggett,

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Structural properties of prion protein protofibrils and fibrils: an experimental assessment of atomic models. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Biochemistry

VOLUME: 45

Page Numbers: 15573-82

Journal Abbreviation: Biochemistry

ISSN: 1520-4995

DAY: 1

MONTH: 12

YEAR: 2006

Structural properties of prion protein protofibrils and fibrils: an experimental assessment of atomic models. Information

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LANGUAGE: eng

NlmUniqueID: 370623

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Grant and Affiliation Information for Structural properties of prion protein protofibrils and fibrils: an experimental assessment of atomic models.

AFFILIATION: Department of Medicinal Chemistry, Biomolecular Structure and Design Program, University of Washington, Seattle, Washington 98195-7610, USA.

Country: United States

AGENCY: United States NIGMS

GRANT: T32 GM-07750

ACRONYM: GM

MEDLINETA: Biochemistry

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