Dataset Information

Polymer-Peptide Conjugates Convert Amyloid into Protein Nanobundles through Fragmentation and Lateral Association.

ABSTRACT: The assembly of proteins into amyloid fibrils has become linked not only with the progression of myriad human diseases, but also important biological functions. Understanding and controlling the formation, structure, and stability of amyloid fibrils is therefore a major scientific goal. Here we utilize electron microscopy-based approaches combined with quantitative statistical analysis to show how recently developed kind of amyloid modulators-multivalent polymer-peptide conjugates (mPPCs)-can be applied to control the structure and stability of amyloid fibrils. In doing so, we demonstrate that mPPCs are able to convert 40-residue amyloid beta fibrils into ordered nanostructures through a combination of fragmentation and bundling. Fragmentation is shown to be consistent with a model where the rate constant of fibril breakage is independent of the fibril length, suggesting a local and specific interaction between fibrils and mPPCs. Subsequent bundling, which was previously not observed, leads to the formation of sheet-like nanostructures which are surprisingly much more uniform than the starting fibrils. These nanostructures have dimensions independent of the molecular weight of the mPPC and retain the molecular-level ordering of the starting amyloid fibrils. Collectively, we reveal quantitative and nanoscopic understanding of how mPPCs can be applied to control amyloid structure and stability, and demonstrate approaches to elucidate nanoscale amyloid phase behavior in the presence of functional macromolecules and other modulators.

SUBMITTER: Smith JW

PROVIDER: S-EPMC7059651 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Polymer-Peptide Conjugates Convert Amyloid into Protein Nanobundles through Fragmentation and Lateral Association.

Smith John W JW Jiang Xing X An Hyosung H Barclay Alexander M AM Licari Giuseppe G Tajkhorshid Emad E Moore Edwin G EG Rienstra Chad M CM Moore Jeffrey S JS Chen Qian Q

ACS applied nano materials 20190910 2

The assembly of proteins into amyloid fibrils has become linked not only with the progression of myriad human diseases, but also important biological functions. Understanding and controlling the formation, structure, and stability of amyloid fibrils is therefore a major scientific goal. Here we utilize electron microscopy-based approaches combined with quantitative statistical analysis to show how recently developed kind of amyloid modulators-multivalent polymer-peptide conjugates (mPPCs)-can be ...[more]

PMID: 32149271

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Dataset Information

Polymer-Peptide Conjugates Convert Amyloid into Protein Nanobundles through Fragmentation and Lateral Association.

Publications

Polymer-Peptide Conjugates Convert Amyloid into Protein Nanobundles through Fragmentation and Lateral Association.

Similar Datasets

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