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Shear-flow induced changes in apolipoprotein C-II conformation and amyloid fibril formation.
MedLine Citation:
PMID:  21476595     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The misfolding and self-assembly of proteins into amyloid fibrils that occurs in several debilitating diseases is affected by a variety of environmental factors including mechanical factors associated with shear flow. We examined the effects of shear flow on amyloid fibril formation by human apolipoprotein (apo) C-II. Shear fields, 150 s-1, 300 s-1 and 500 s-1, accelerated the rate of apoC-II fibril formation (1 mg/ml) approximately 5 - 10 fold. Fibrils produced at shear rates of 150 s-1 and 300 s-1 were similar to the twisted ribbon fibrils formed in the absence of shear, while at 500 s-1, tangled rope-like structures were observed. The mechanism of the shear-induced acceleration of amyloid fibril formation was investigated at low apoC-II concentrations (50 µg/ml) where fibril formation does not occur. Circular dichroism and tryptophan fluorescence indicated that shear induced an irreversible change in apoC-II secondary structure. Fluorescence resonance energy transfer experiments using the single tryptophan residue in apoC-II as the donor and covalently attached acceptors showed that shear flow increased the distance between the donor and acceptor molecules. Shear-induced higher oligomeric species were identified by sedimentation velocity experiments using fluorescence detection, while fibril seeding experiments showed that species formed during shear-flow are on the fibril formation pathway. These studies suggest that physiological shear-flow conditions and conditions experienced during protein manufacturing can exert significant effects on protein conformation leading to protein misfolding, aggregation, and amyloid fibril formation.
Authors:
Chai Lean Teoh; Innocent B Bekard; Peter Asimakis; Michael D W Griffin; Timothy W Ryan; Dave Edwin Dunstan; Geoffrey John Howlett
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-4-9
Journal Detail:
Title:  Biochemistry     Volume:  -     ISSN:  1520-4995     ISO Abbreviation:  -     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-4-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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