title: Complex interactions between bovine plasminogen and streptococcal plasminogen activator PauA.
abstract: The interactions between bovine plasminogen and the streptococcal plasminogen activator PauA that culminate in the generation of plasmin are not fully understood. Formation of an equimolar activation complex comprising PauA and plasminogen by non-proteolytic means is a prerequisite to the recruitment of substrate plasminogen; however the determinants that facilitate these interactions have yet to be defined. A mutagenesis strategy comprising nested deletions and random point substitutions indicated roles for both amino and carboxyl-terminal regions of PauA and identified further essential residues within the alpha domain of the plasminogen activator. A critical region within the alpha domain was identified using non-overlapping PauA peptides to block the interaction between PauA and bovine plasminogen, preventing formation of the activation complex. Homology modelling of the activation complex based upon the known structures of streptokinase complexed with human plasmin supported these findings by placing critical residues in close proximity to the plasmin component of the activation complex.
authors.affiliation: Institute for Animal Health, Compton Laboratory, Compton, Berkshire, RG20 7NN, UK. phil.ward@bbsrc.ac.uk
authors.forename: Philip N
authors.initials: PN
authors.lastname: Ward
authors.forename: Terence R
authors.initials: TR
authors.lastname: Field
authors.forename: Everett L
authors.initials: EL
authors.lastname: Rosey
authors.forename: Abu-Bakr
authors.initials: AB
authors.lastname: Abu-Median
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Lincoln
authors.forename: James A
authors.initials: JA
authors.lastname: Leigh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D002417:Cattle; D017931:DNA Primers; D008969:Molecular Sequence Data; D016296:Mutagenesis; D010958:Plasminogen / Q000378:metabolism*; D011485:Protein Binding; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid
chemical_list: D001426:Bacterial Proteins; D017931:DNA Primers; C121687:PauA protein, Streptococcus uberis; D010958:Plasminogen