title: 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.
authors.affiliation: Department of Chemistry, Crystal and Structural Chemistry, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, the Netherlands.
authors.forename: Dennis X
authors.initials: DX
authors.lastname: Beringer
authors.forename: Marcel J E
authors.initials: MJ
authors.lastname: Fischer
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Meeldijk
authors.forename: Elly G
authors.initials: EG
authors.lastname: van Donselaar
authors.forename: Nico J
authors.initials: NJ
authors.lastname: de Mol
authors.forename: Loes M J
authors.initials: LM
authors.lastname: Kroon-Batenburg
mesh_terms: D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001665:Binding Sites; D015374:Biosensing Techniques; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D020349:Surface Plasmon Resonance; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D058228:Islet Amyloid Polypeptide; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D010959:Tissue Plasminogen Activator; D008239:Lysine