Heparin accelerates gelsolin amyloidogenesis.

ABSTRACT: The chemical environment of the extracellular matrix may influence the tissue-selective deposition observed there in gelsolin amyloid disease. Previously, we have identified the proteases that generate the amyloidogenic fragments from the full-length gelsolin variants and demonstrated that heparin is capable of accelerating gelsolin amyloidogenesis. Herein, we identify the structural features of heparin that promote the 8 kDa disease-associated gelsolin fragments (residues 173-243) generated at the cell surface to form amyloid. In conjunction with electron microscopy analyses, our kinetic studies demonstrate that heparin efficiently accelerates the formation of gelsolin amyloid by enabling intermolecular beta-sheet formation. The use of heparin analogues reveals that sulfation is important

SUBMITTER: Suk JY 

PROVIDER: S-EPMC2657342 | biostudies-literature | 2006 Feb

REPOSITORIES: biostudies-literature