The staphylocoagulase family of zymogen activator and adhesion proteins.
Staphylocoagulase (SC) secreted by Staphylococcus aureus is a potent non-proteolytic activator of the blood coagulation zymogen prothrombin and the prototype of a newly established zymogen activator and adhesion protein (ZAAP) family. The conformationally activated SC.prothrombin complex specifically cleaves fibrinogen to fibrin, which propagates the growth of bacteria-fibrin-platelet vegetations in acute bacterial endocarditis. Our recent 2.2 A X-ray crystal structures of an active SC fragment [SC(1-325)] bound to the prothrombin zymogen catalytic domain, prethrombin 2, demonstrated that SC(1-325) represents a new type of non-proteolytic activator with a unique fold. The observed insertion of the SC(1-325) N-terminus into the 'Ile 16' cleft of prethrombin 2, which triggers the activating conformational change, provided the first unambiguous structural evidence for the 'molecular sexuality' mechanism of non-proteolytic zymogen activation. Based on the SC(1-325) fold, a new family of bifunctional zymogen activator and adhesion proteins was identified that possess N-terminal domains homologous to SC(1-325) and C-terminal domains that mediate adhesion to plasma or extracellular matrix proteins. Further investigation of the ZAAP family may lead to new insights into the mechanisms of bacterial factors that hijack zymogens of the human blood coagulation and fibrinolytic systems to promote and disseminate endocarditis and other infectious diseases.
Panizzi
P
P
Department of Pathology, Vanderbilt University School of Medicine, C3321A Medical Center North, 37232-2561, Nashville, USA.
Friedrich
R
R
Fuentes-Prior
P
P
Bode
W
W
Bock
P E
PE
D003030:Coagulase / Q000737:chemistry / Q000378:metabolism*; D004697:Endocarditis, Bacterial / Q000209:etiology; D004792:Enzyme Precursors / Q000737:chemistry / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011487:Protein Conformation; D011516:Prothrombin / Q000737:chemistry / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D013203:Staphylococcal Infections / Q000209:etiology; D013211:Staphylococcus aureus / Q000201:enzymology* / Q000472:pathogenicity; D013379:Substrate Specificity
D003030:Coagulase; D004792:Enzyme Precursors; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; C028254:von Willebrand factor receptor; D011516:Prothrombin; D005340:Fibrinogen