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Annular oligomeric amyloid intermediates observed by in situ atomic force microscopy
Min Zhu1, Shubo Han, Feimeng Zhou
1Department of Chemistry and Biochemistry, University of California, Santa Cruz 95064, USA.
The Journal of Biological Chemistry
|April 2, 2004
Summary
Toxic oligomeric intermediates, not just fibrils, may cause amyloidosis. Real-time atomic force microscopy revealed diverse intermediate structures during immunoglobulin light chain aggregation.
Area of Science:
- Biochemistry
- Molecular Biology
- Biophysics
Background:
- Amyloidoses involve misfolded proteins forming insoluble deposits.
- Traditionally, amyloid fibrils were considered the primary toxic species.
- Emerging evidence suggests soluble oligomers may be more pathogenic.
Purpose of the Study:
- To investigate the in situ aggregation pathway of an amyloidogenic immunoglobulin light chain.
- To characterize the morphology and formation of oligomeric intermediates.
- To understand the influence of environmental conditions on aggregation.
Main Methods:
- Real-time in situ atomic force microscopy was employed.
- Aggregation of immunoglobulin light chain was monitored in aqueous solution.
- Incubation conditions, including pH and ionic strength, were varied.
Main Results:
- Diverse oligomeric intermediates were observed during aggregation.
- Morphologies included annular and torus-shaped species.
- The nature and population of intermediates depended on pH and ionic strength.
Conclusions:
- Protein aggregation is a complex process with multiple intermediate species.
- Oligomeric intermediates play a critical role in amyloid formation.
- Environmental factors significantly influence the aggregation pathway and intermediate populations.