{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T15:26:03Z","timestamp":1793028363397,"version":"4.5.0"},"reference-count":59,"publisher":"Georg Thieme Verlag KG","issue":"11","funder":[{"name":"Bayer Hemophilia Awards Program"},{"name":"Landsteiner Foundation for Blood Transfusion","award":["grant. no. 1451"],"award-info":[{"award-number":["grant. no. 1451"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The venom of the Australian snake Pseudonaja textilis comprises powerful prothrombin activators consisting of factor X (v-ptFX)- and factor V-like proteins. While all vertebrate liver-expressed factor X (FX) homologs, including that of P. textilis, comprise an activation peptide of approximately 45 to 65 residues, the activation peptide of v-ptFX is significantly shortened to 27 residues. In this study, we demonstrate that exchanging the human FX activation peptide for the snake venom ortholog impedes proteolytic cleavage by the intrinsic factor VIIIa\u2013factor IXa tenase complex. Furthermore, our findings indicate that the human FX activation peptide comprises an essential binding site for the intrinsic tenase complex. Conversely, incorporation of FX into the extrinsic tissue factor\u2013factor VIIa tenase complex is completely dependent on exosite-mediated interactions. Remarkably, the shortened activation peptide allows for factor V-dependent prothrombin conversion while in the zymogen state. This indicates that the active site of FX molecules comprising the v-ptFX activation peptide partially matures upon assembly into a premature prothrombinase complex. Taken together, the shortened activation peptide is one of the remarkable characteristics of v-ptFX that has been modified from its original form, thereby transforming FX into a powerful procoagulant protein. Moreover, these results shed new light on the structural requirements for serine protease activation and indicate that catalytic activity can be obtained without formation of the characteristic Ile16\u2013Asp194 salt bridge via modification of the activation peptide.<\/jats:p>","DOI":"10.1055\/s-0040-1715441","type":"journal-article","created":{"date-parts":[[2020,8,20]],"date-time":"2020-08-20T20:27:45Z","timestamp":1597955265000},"page":"1512-1523","source":"Crossref","is-referenced-by-count":13,"title":["Evolutionary Adaptations in Pseudonaja Textilis Venom Factor X Induce Zymogen Activity and Resistance to the Intrinsic Tenase Complex"],"prefix":"10.1055","volume":"120","author":[{"given":"Mark","family":"Schreuder","sequence":"additional","affiliation":[{"name":"Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geraldine","family":"Poenou","sequence":"additional","affiliation":[{"name":"Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"},{"name":"AP\u2013HP, H\u00f4pital Louis Mourier, Colombes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viola J. F.","family":"Strijbis","sequence":"additional","affiliation":[{"name":"Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ka Lei","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter H.","family":"Reitsma","sequence":"additional","affiliation":[{"name":"Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mettine H. A.","family":"Bos","sequence":"additional","affiliation":[{"name":"Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2020,8,20]]},"reference":[{"key":"ref1","first-page":"1915","volume-title":"Molecular biology and biochemistry of the coagulation factors and pathways of hemostasis","author":"M HA Bos","year":"2016"},{"issue":"27","key":"ref2","doi-asserted-by":"crossref","first-page":"18627","DOI":"10.1074\/jbc.M802205200","article-title":"The conformational switch from the factor X zymogen to protease state mediates exosite expression and prothrombinase assembly","volume":"283","author":"R Toso","year":"2008","journal-title":"J Biol Chem"},{"issue":"05","key":"ref3","first-page":"756","article-title":"The role of the factor X activation peptide: a deletion mutagenesis 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