Tissue-type plasminogen activator binds to Aβ and AIAPP amyloid fibrils with multiple domains

Abstract

Binding of tissue-type plasminogen activator (tPA) to amyloid and denatured proteins is reported in a number of studies. The binding site has been mapped previously to the finger domain of tPA. In this study, tPA and truncated tPA constructs, lacking the finger domain, were tested for their ability to bind to Aβ and AIAPP amyloid-like fibrils. Surface plasmon resonance experiments and pull-down assays clearly show that indeed tPA binds, but that the finger domain is not essential. Another possible binding mechanism via the lysine binding site on the kringle 2 domain was also not crucial for the binding. Immuno-electron microscopy studies show that tPA binds to fibril sides. This study shows that, besides the finger domain, other domains in tPA are involved in amyloid binding.

• Amyloid interaction
• amyloid pull-down assay
• immuno-electron microscopy
• surface plasmon resonance
• tissue-type plasminogen activator

Acknowledgements

We thank Dr Martijn F. B. G. Gebbink for the useful discussions and suggestions during this study.