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Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Cross-beta-sheet structure in amyloid fiber formation.
1Department of Biological Sciences and Physics and Space Sciences, Florida Institute of Technology, Melbourne, FL 32901, USA. shaohua@fit.edu
The Journal of Physical Chemistry. B
|August 27, 2009
Summary
Protein aggregation into amyloid fibers involves a two-stage process. The Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory explains how colloidal spheres form, misfold, and assemble into mature amyloid fibers.
Area of Science:
- Biophysics
- Materials Science
- Structural Biology
Background:
- Protein aggregation into amyloid fibers is linked to conformational changes from native states to cross-beta-sheet structures.
- The necessity of this secondary structure change for fiber formation is not fully understood.
- Current evidence suggests a two-stage aggregation process involving colloidal spheres and subsequent chain formation.
Purpose of the Study:
- To apply the Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory to quantitatively analyze protein aggregation into amyloid fibers.
- To elucidate the mechanisms underlying the two distinct stages of amyloid fiber formation.
Main Methods:
- Application of the Derjaguin, Landau, Verwey, and Overbeek (DLVO) theory for colloidal interaction analysis.
- Analysis of atomic force microscopy and transmission electron microscopy data.
- Utilizing energy analysis and X-ray diffraction data.
Main Results:
- DLVO theory explains monomer aggregation into uniform-sized colloidal spheres due to charge repulsion limiting growth.
- Misfolding into hairpin loops and subsequent U-shaped trough formation with cross-alpha-sheet structure and dipole moment were observed.
- Charge-dipole interactions drive sphere aggregation into linear chains, with peptide strands oriented perpendicularly to the chain axis.
Conclusions:
- The study provides a quantitative biophysical model for amyloid fiber formation using DLVO theory.
- The conformational change to cross-alpha-sheet and subsequent evolution to cross-beta-sheet is driven by colloidal interactions and thermodynamic stability.
- This research offers novel insights into the fundamental processes of protein aggregation and amyloidogenesis.
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