Related Experiment Video
Updated: Jun 8, 2026
14:55
Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Amyloid structure and assembly: insights from scanning transmission electron microscopy
Claire Goldsbury1, Ulrich Baxa, Martha N Simon
1The Brain and Mind Research Institute, University of Sydney, NSW 2006, Australia.
Journal of Structural Biology
|September 28, 2010
Summary
Scanning transmission electron microscopy (STEM) measures amyloid fibril mass-per-length, revealing complex assembly pathways and polymorphisms. This technique aids structural modeling for diseases like Alzheimer's.
Area of Science:
- Biophysics
- Structural Biology
- Biochemistry
Background:
- Amyloid fibrils are protein aggregates linked to diseases like Alzheimer's and type II diabetes.
- Similar structures, such as yeast prions, are involved in inherited traits.
- Scanning transmission electron microscopy (STEM) is a key tool for studying amyloid structures.
Purpose of the Study:
- To review the contributions and limitations of STEM in investigating amyloid assembly.
- To explore STEM's role in understanding fibril polymorphisms and structural models.
- To highlight STEM's unique ability to measure mass-per-length (MPL) of individual amyloid filaments.
Main Methods:
- Utilizing scanning transmission electron microscopy (STEM) for mass-per-length (MPL) measurements.
- Analyzing both in vitro assembled and ex vivo amyloid samples.
- Integrating STEM data with high-resolution methods like solid-state nuclear magnetic resonance (NMR) and electron paramagnetic resonance (EPR).
Main Results:
- STEM mass measurements illuminate hierarchical relationships in amyloid fibril assembly.
- Demonstrated that polymorphic fibrils and globular oligomers can co-assemble from a single polypeptide.
- MPL data provides constraints for molecular model building of amyloid structures.
Conclusions:
- STEM is crucial for understanding amyloid assembly pathways and structural diversity.
- The technique enables direct mass measurements, offering unique insights into fibril formation.
- STEM, combined with other methods, advances the molecular modeling of amyloid aggregates.
Related Concept Videos
01:07Electron Microscope Tomography and Single-particle Reconstruction
Transmission electron microscopy (TEM) can be used to determine the 3D structure of biological samples with the help of techniques such as electron microscope tomography and single-particle reconstruction. While single-particle reconstruction can examine macromolecules and macromolecular complexes in vitro conditions only, tomography permits the study of cell components or small cells in vivo.
Electron Tomography
Electron tomography can be performed either in TEM or STEM (scanning transmission...
Electron Tomography
Electron tomography can be performed either in TEM or STEM (scanning transmission...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
03:03Amyloid Fibrils
Amyloid fibrils are aggregates of misfolded proteins. Under most circumstances, misfolded proteins are either refolded by chaperone proteins or degraded by the proteasome. However, in the case of a mutation or a disease, these proteins can accumulate to form large clusters and often further assemble to form elongated fibers, called fibrils.
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
Amyloid deposits were observed as early as 1639 in the liver and the spleen. In 1854, Rudolph Virchow performed iodine staining, normally used to...
02:41Protein Complex Assembly
Proteins can form homomeric complexes with another unit of the same protein or heteromeric complexes with different types. Most protein complexes self-assemble spontaneously via ordered pathways, while some proteins need assembly factors that guide their proper assembly. Despite the crowded intracellular environment, proteins usually interact with their correct partners and form functional complexes.
Many viruses self-assemble into a fully functional unit using the infected host cell to...
Many viruses self-assemble into a fully functional unit using the infected host cell to...
01:28Cryo-electron Microscopy
Conventional electron microscopy (EM) involves dehydration, fixation, and staining of biological samples, which distorts the native state of biological molecules and results in several artifacts. Also, the high-energy electron beam damages the sample and makes it difficult to obtain high-resolution images. These issues can be addressed using cryo-EM, which uses frozen samples and gentler electron beams. The technique was developed by Jacques Dubochet, Joachim Frank, and Richard Henderson, for...