Document Detail


Revealing different aggregation pathways of amyloidogenic proteins by ultrasound velocimetry.
MedLine Citation:
PMID:  18192359     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this work, we performed a detailed thermodynamic study, including ultrasound velocimetry, densimetry, calorimetry, and FTIR spectroscopy, of an aggregation-prone protein (insulin) under different salt-screening conditions to gain a deeper insight into the scenario of physicochemical events during its temperature-induced unfolding and aggregation reactions. Differences in aggregation and fibrillization pathways are reflected in changes of the partial molar volume, the coefficients of thermal expansion and compressibility, and the infrared spectral properties of the protein. Combining all experimental data allows setting up a scheme for the temperature-dependent insulin aggregation reaction in the presence and absence of NaCl. As revealed by complementary atomic force microscopy studies, under charge-screening conditions, a process involving structural reorganization, ripening, and formation of more compact nuclei from amorphous oligomers is involved in the formation of mature fibrillar morphologies. In this work, our focus was to put forward a comprehensive discussion of the use of ultrasound velocimetry in disentangling different aggregation pathways. In fact, ultrasound velocimetry proved to be very sensitive to changes in aggregation pathway, highlighting the importance of density and compressibility changes in the different aggregation and fibrillization reactions of the protein.
Authors:
Vytautas Smirnovas; Roland Winter
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-01-11
Journal Detail:
Title:  Biophysical journal     Volume:  94     ISSN:  1542-0086     ISO Abbreviation:  Biophys. J.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-27     Completed Date:  2008-05-12     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3241-6     Citation Subset:  IM    
Affiliation:
University of Dortmund, Department of Chemistry, Physical Chemistry I, Biophysical Chemistry, Dortmund, Germany.
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MeSH Terms
Descriptor/Qualifier:
Amyloid / chemistry*,  ultrastructure*
Binding Sites
Computer Simulation
Dimerization
Models, Chemical*
Models, Molecular*
Multiprotein Complexes / chemistry*,  ultrastructure*
Protein Binding
Ultrasonics
Chemical
Reg. No./Substance:
0/Amyloid; 0/Multiprotein Complexes
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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