Type-1 inhibitor of plasminogen activators. Distinction between latent, activated and reactive centre-cleaved forms with thermal stability and monoclonal antibodies.
Type-1 inhibitor of plasminogen activators (PAI-1) occurs in purified preparations in a latent form that can be activated with denaturants; in vivo, latency is prevented by binding to vitronectin. We have compared latent, denaturant-activated and reactive centre-cleaved human PAI-1 with respect to thermal stability and affinity to monoclonal antibodies. By both criteria, latent and cleaved PAI-1 are very similar or indistinguishable, and clearly different from active PAI-1. Our findings suggest that the conformations of latent and reactive centre-cleaved PAI-1 are similar and resemble the so-called relaxed (R) serpin conformation, while that of active PAI-1 is different and resembles the stressed (S) serpin conformation.
Munch
M
M
Department of Molecular Biology, University of Arhus, Denmark.
Heegaard
C
C
Jensen
P H
PH
Andreasen
P A
PA
D000911:Antibodies, Monoclonal; D001665:Binding Sites; D001666:Binding Sites, Antibody; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G; D008958:Models, Molecular; D015849:Plasminogen Inactivators / Q000097:blood / Q000737:chemistry* / Q000302:isolation & purification; D011487:Protein Conformation; D013816:Thermodynamics
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D015849:Plasminogen Inactivators