Article

Annular oligomeric amyloid intermediates observed by in situ atomic force microscopy.

Department of Chemistry and Biochemistry, University of California, Santa Cruz 95064, USA.
Journal of Biological Chemistry (impact factor: 4.77). 07/2004; 279(23):24452-9. DOI:10.1074/jbc.M400004200 pp.24452-9
Source: PubMed

ABSTRACT Amyloidoses and related protein deposition diseases involve the transformation of normally soluble proteins into insoluble deposits, usually fibrillar in nature. Although it was originally assumed that the fibrils were the toxic species, this assumption has recently been called into question. Accumulating evidence in several systems suggests that oligomeric intermediates on the aggregation pathway may be toxic. In the present study we used in situ atomic force microscopy to monitor aggregation in aqueous solution in real time. The sample used was an amyloidogenic immunoglobulin light chain, involved in AL or light chain amyloidosis. The nature of the observed oligomeric intermediates was dependent on the conditions of incubation, especially pH and ionic strength. Several different aggregation intermediates with a variety of morphologies, including annular or torus-shaped species, were observed. The data indicate that protein aggregation can be very complex, involving a variety of different oligomeric intermediates whose population will be determined by the kinetic and thermodynamic competition between them.

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Keywords

Accumulating evidence
 
aggregation
 
aggregation pathway
 
amyloidogenic immunoglobulin light chain
 
aqueous solution
 
different aggregation intermediates
 
different oligomeric intermediates
 
ionic strength
 
kinetic
 
morphologies
 
observed oligomeric intermediates
 
oligomeric intermediates
 
protein aggregation
 
protein deposition diseases
 
real time
 
situ atomic force microscopy
 
soluble proteins
 
thermodynamic competition
 
torus-shaped species
 
toxic species
 

Min Zhu