Article

Massively parallel genetic perturbation reveals the energetic architecture of an amyloid beta nucleation reaction

2024-07-24

Abstract excerpt

Amyloid protein aggregates are pathological hallmarks of more than fifty human diseases but how soluble proteins nucleate to form amyloids is poorly understood. Here we use combinatorial mutagenesis, a kinetic selection assay, and machine learning to massively perturb the energetics of the nucleation reaction of amyloid beta (Aβ42), the protein that aggregates in Alzheimer’s disease. In total, we quantify the nucl...

Topics

Open a Topic to create a Post that cites this publication.

Identifiers and source

Literature Corpus work: 9b409766-36bf-5c90-8250-9fa87fa41b17
DOI: 10.1101/2024.07.24.604935

Open publication

Related research

Semantic proximity does not establish scientific evidence.

Click a neighbor to travelStep 1 · 12 closest

Massively parallel genetic perturbation reveals the energetic architecture of an amyloid beta nucleation reactionDOI 10.1101/2024.07.24.604935Read

Massively parallel genetic perturbation suggests the energetic structure of an amyloid-β transition stateSemantic proximity Read

The genetic landscape for amyloid beta fibril nucleation accurately discriminates familial Alzheimer's disease mutations.Semantic proximity Read

The genetic landscape for amyloid beta fibril nucleation accurately discriminates familial Alzheimer’s disease mutationsSemantic proximity Read

Exploring the origins of nucleation.Semantic proximity Read

Massively parallel quantification of mutational impact on IAPP amyloid formation.Semantic proximity Read

An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleationSemantic proximity Read

An atlas of amyloid aggregation: the impact of substitutions, insertions, deletions and truncations on amyloid beta fibril nucleationSemantic proximity Read

Massively parallel quantification of mutational impact on IAPP amyloid formationSemantic proximity Read

Massive experimental quantification of amyloid nucleation allows interpretable deep learning of protein aggregationSemantic proximity Read

Towards mechanistic models of mutational effects: Deep Learning on Alzheimer’s Aβ peptideSemantic proximity Read

Structural defects in amyloid-β fibrils drive secondary nucleationSemantic proximity Read

Probing the energy landscape of α-Synuclein amyloid fibril formation by systematic K-to-Q mutagenesisSemantic proximity Read