Document Detail

Ionic strength effects on amyloid formation by amylin are a complicated interplay among Debye screening, ion selectivity, and Hofmeister effects.
MedLine Citation:
PMID:  23016872     Owner:  NLM     Status:  MEDLINE    
Amyloid formation plays a role in a wide range of human diseases. The rate and extent of amyloid formation depend on solution conditions, including pH and ionic strength. Amyloid fibrils often adopt structures with parallel, in-register β-sheets, which generate quasi-infinite arrays of aligned side chains. These arrangements can lead to significant electrostatic interactions between adjacent polypeptide chains. The effect of ionic strength and ion composition on the kinetics of amyloid formation by islet amyloid polypeptide (IAPP) is examined. IAPP is a basic 37-residue polypeptide responsible for islet amyloid formation in type 2 diabetes. Poisson-Boltzmann calculations revealed significant electrostatic repulsion in a model of the IAPP fibrillar state. The kinetics of IAPP amyloid formation are strongly dependent on ionic strength, varying by a factor of >10 over the range of 20-600 mM NaCl at pH 8.0, but the effect is not entirely due to Debye screening. At low ionic strengths, the rate depends strongly on the identity of the anion, varying by a factor of nearly 4, and scales with the electroselectivity series, implicating anion binding. At high ionic strengths, the rate varies by only 8% and scales with the Hofmeister series. At intermediate ionic strengths, no clear trend is detected, likely because of the convolution of different effects. The effects of salts on the growth phase and lag phase of IAPP amyloid formation are strongly correlated. At pH 5.5, where the net charge on IAPP is higher, the effect of different anions scales with the electroselectivity series at all salt concentrations.
Peter J Marek; Vadim Patsalo; David F Green; Daniel P Raleigh
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-16
Journal Detail:
Title:  Biochemistry     Volume:  51     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2013-01-18     Completed Date:  2013-03-19     Revised Date:  2013-11-04    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8478-90     Citation Subset:  IM    
Department of Chemistry, Stony Brook University, Stony Brook, NY 11794, USA.
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MeSH Terms
Amino Acid Sequence
Amyloid / chemistry,  metabolism*,  ultrastructure
Ions / chemistry,  metabolism
Islet Amyloid Polypeptide / chemistry,  metabolism*,  ultrastructure
Models, Molecular
Molecular Sequence Data
Osmolar Concentration
Grant Support
Reg. No./Substance:
0/Amyloid; 0/Ions; 0/Islet Amyloid Polypeptide

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

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