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Biochemical Purification and Proteomic Characterization of Amyloid Fibril Cores from the Brain
Published on: April 28, 2022
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3D structure determination of amyloid fibrils using solid-state NMR spectroscopy
Antoine Loquet1, Nadia El Mammeri1, Jan Stanek2
1Institute of Chemistry and Biology of Membranes and Nanoobjects, Institut Européen de Chimie et Biologie (CNRS UMR 5248, Université de Bordeaux), 33600 Pessac, France.
Methods (San Diego, Calif.)
|April 9, 2018
Summary
Amyloid structures, known for their cross-β architecture, are implicated in both neurodegenerative diseases and normal biological functions. Solid-state NMR spectroscopy (SSNMR) is a key technique for determining their atomic-level structures and interactions.
Area of Science:
- Biophysics
- Structural Biology
- Neuroscience
Background:
- The amyloid fold, characterized by a cross-β architecture, is a stable protein conformation with roles in both disease and normal biological processes.
- Functional amyloids, distinct from pathological amyloid fibrils in neurodegenerative disorders, are increasingly recognized for their roles in native biological functions.
- The insoluble and heterogeneous nature of amyloid fibrils presents significant challenges for atomic-level structural characterization using traditional biophysical methods.
Purpose of the Study:
- To review emerging concepts and state-of-the-art methods for assessing amyloid structures and interactions.
- To highlight the application of solid-state NMR spectroscopy (SSNMR) in elucidating the structural basis of amyloid formation and function.
- To discuss advancements in SSNMR techniques for characterizing both pathological and functional amyloid assemblies.
Main Methods:
- Solid-state NMR spectroscopy (SSNMR) is presented as a powerful technique for atomic-level structural investigations of amyloid fibrils.
- Strategies discussed include protein isotope labeling, NMR resonance assignment, and distance restraint determination for structural calculations.
- Advancements in 3D structure calculation of amyloid fibrils using SSNMR approaches are detailed.
Main Results:
- SSNMR has enabled breakthroughs in understanding amyloid polymorphism and its role in disease.
- Atomic-level 3D structure determination of amyloid fibrils has been achieved using SSNMR.
- Studies on functional amyloids using SSNMR are providing new insights into their biological roles.
Conclusions:
- SSNMR is a pivotal technique for characterizing the structure and interactions of amyloid entities at atomic resolution.
- The application of SSNMR is crucial for deciphering the structural mechanisms underlying both amyloid-related diseases and functional amyloid roles.
- Continued development of SSNMR strategies will further advance our understanding of the diverse functions of the amyloid fold.
Keywords:
Amyloid fibrilsIsotopic labellingPrionsProtein aggregationProton detectionSolid-state NMRStructural biologyStructure calculationMore Related Videos
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