J Biol Chem. 2003 Aug 8 [Epub ahead of print].
Bouma B, Kroon-Batenburg LM, Wu YP, Brunjes B, Posthuma G, Kranenburg O, De Groot PG, Voest EE, Gebbink MF.
Medical Oncology, University Medical Center Utrecht, Utrecht 3584 CX.
Amyloid fibrils are components of proteinaceous plaques that are associated with conformational diseases such as Alzheimers disease, transmissible spongiform encephalopathies and familial amyloidosis. Amyloid polypeptides share a specific quarternary structure element known as cross-(beta} structure. Commonly, fibrillar aggregates are modified by advanced glycation endproducts (AGE).
In addition, AGE formation itself induces protein aggregation. Both amyloid proteins and protein-AGE adducts bind multiligand receptors, such as receptor for AGE, CD36, and Scavenger receptors A and B type I, and for the serine protease tissue-type plasminogen activator (tPA).
Based on these observations, we hypothesized that glycation induces refolding of globular proteins, accompanied by formation of cross-beta structure. Using transmission electron microscopy we demonstrate here that glycated albumin condensates into fibrous or amorphous aggregates. These aggregates bind to amyloid-specific dyes Congo red and Thioflavin T, and to tPA. In contrast to globular albumin, glycated albumin contains amino-acid residues in (beta}-sheet conformation, as measured with circular dichroism spectropolarimetry.
Moreover, it displays cross-beta structure, as determined with X-ray fibre diffraction. We conclude that glycation induces refolding of initially globular albumin into amyloid fibrils comprising cross-beta structure. This would explain how glycated ligands and amyloid ligands can bind to the same multiligand cross-beta structure receptors and to tPA.
PMID: 12909637 [PubMed – as supplied by publisher]