Format

Send to

Choose Destination

See 1 citation found by title matching your search:

J Biol Chem. 2011 Jul 1;286(26):22894-904. doi: 10.1074/jbc.M110.215814. Epub 2011 May 9.

Mechanism of amylin fibrillization enhancement by heparin.

Author information

1
Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut 06269-3125, USA.

Abstract

We characterized the interaction of amylin with heparin fragments of defined length, which model the glycosaminoglycan chains associated with amyloid deposits found in type 2 diabetes. Binding of heparin fragments to the positively charged N-terminal half of monomeric amylin depends on the concentration of negatively charged saccharides but is independent of oligosaccharide length. By contrast, amylin fibrillogenesis has a sigmoidal dependence on heparin fragment length, with an enhancement observed for oligosaccharides longer than four monomers and a leveling off of effects beyond 12 monomers. The length dependence suggests that the negatively charged helical structure of heparin electrostatically complements the positively charged surface of the fibrillar amylin cross-β structure. Fluorescence resonance energy transfer and total internal reflection fluorescence microscopy experiments indicate that heparin associates with amylin fibrils, rather than enhancing fibrillogenesis catalytically. Short heparin fragments containing two- or eight-saccharide monomers protect against amylin cytotoxicity toward a MIN6 mouse cell model of pancreatic β-cells.

PMID:
21555785
PMCID:
PMC3123057
DOI:
10.1074/jbc.M110.215814
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center