title: Structural basis of the cofactor function of denatured albumin in plasminogen activation by tissue-type plasminogen activator.
abstract: Certain denatured proteins function as cofactors in the activation of plasminogen by tissue-type plasminogen activator. The present study approached the structural requirements for the cofactor activity of a model protein (human serum albumin). Heat denaturation of 100-230 microM albumin (80 degrees C and 60-90 min) reproducibly yielded aggregates with radius in the range of 10-150 nm. The major determinant of the cofactor potency was the size of the aggregates. The increase of particle size correlated with the cofactor activity, and there was a minimal requirement for the size of the cofactor (about 10 nm radius). Similar to other proteins, the molecular aggregates with cofactor function contained a significant amount of antiparallel intermolecular beta-sheets. Plasmin pre-digestion increased the cofactor efficiency (related to C-terminal lysine exposure) and did not affect profoundly the structure of the aggregates, suggesting a long-lasting and even a self-augmenting cofactor function of the denatured protein.
authors.affiliation: Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Galántai
authors.forename: Károly
authors.initials: K
authors.lastname: Módos
authors.forename: Judit
authors.initials: J
authors.lastname: Fidy
authors.forename: Krasimir
authors.initials: K
authors.lastname: Kolev
authors.forename: Raymund
authors.initials: R
authors.lastname: Machovich
mesh_terms: D052160:Benzothiazoles; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D010316:Particle Size; D010958:Plasminogen / Q000378:metabolism*; D011489:Protein Denaturation; D012709:Serum Albumin / Q000737:chemistry* / Q000378:metabolism*; D013844:Thiazoles / Q000494:pharmacology; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
chemical_list: D052160:Benzothiazoles; D012709:Serum Albumin; D013844:Thiazoles; C009462:thioflavin T; D010958:Plasminogen; D010959:Tissue Plasminogen Activator