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Determination of amyloid core structure using chemical shifts.

ABSTRACT: Amyloid fibrils are the pathological hallmark of a large variety of neurodegenerative disorders. The structural characterization of amyloid fibrils, however, is challenging due to their non-crystalline, heterogeneous, and often dynamic nature. Thus, the structure of amyloid fibrils of many proteins is still unknown. We here show that the structure calculation program CS-Rosetta can be used to obtain insight into the core structure of amyloid fibrils. Driven by experimental solid-state NMR chemical shifts and taking into account the polymeric nature of fibrils CS-Rosetta allows modeling of the core of amyloid fibrils. Application to the Y145X stop mutant of the human prion protein reveals a left-handed ?-helix.

SUBMITTER: Skora L

PROVIDER: S-EPMC3575924 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Determination of amyloid core structure using chemical shifts.

Skora Lukasz L Zweckstetter Markus M

Protein science : a publication of the Protein Society 20121026 12

Amyloid fibrils are the pathological hallmark of a large variety of neurodegenerative disorders. The structural characterization of amyloid fibrils, however, is challenging due to their non-crystalline, heterogeneous, and often dynamic nature. Thus, the structure of amyloid fibrils of many proteins is still unknown. We here show that the structure calculation program CS-Rosetta can be used to obtain insight into the core structure of amyloid fibrils. Driven by experimental solid-state NMR chemic ...[more]

PMID: 23033250

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