{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:46:03Z","timestamp":1790732763426,"version":"4.1.0"},"reference-count":58,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>\n              The Australian snake venom ptFV (\n              <jats:italic>Pseudonaja textilis<\/jats:italic>\n              venom-derived factor V) variant retains cofactor function despite APC (activated protein C)-dependent proteolysis. Here, we aimed to unravel the mechanistic principles by determining the role of the absent Arg306 cleavage site that is required for the inactivation of FVa (mammalian factor Va).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>Our findings show that in contrast to human FVa, APC-catalyzed proteolysis of ptFVa at Arg306 and Lys507 does not abrogate ptFVa cofactor function. Remarkably, the structural integrity of APC-proteolyzed ptFVa is maintained indicating that stable noncovalent interactions prevent A2-domain dissociation. Using Molecular Dynamics simulations, we uncovered key regions located in the A1 and A2 domain that may be at the basis of this remarkable characteristic.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Taken together, we report a completely novel role for uniquely adapted regions in ptFVa that prevent A2 domain dissociation. As such, these results challenge our current understanding by which strict regulatory mechanisms control FVa activity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.121.316038","type":"journal-article","created":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T09:01:02Z","timestamp":1624525262000},"page":"2263-2276","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["ptFVa (\n            <i>Pseudonaja Textilis<\/i>\n            Venom-Derived Factor Va) Retains Structural Integrity Following Proteolysis by Activated Protein C"],"prefix":"10.1161","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2196-0943","authenticated-orcid":true,"given":"Mark","family":"Schreuder","sequence":"first","affiliation":[{"name":"Division of Thrombosis and Hemostasis, Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, the Netherlands (M.S., K.L.C., P.H.R., M.H.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosong","family":"Liu","sequence":"additional","affiliation":[{"name":"Maastricht University, Department of Biochemistry, the Netherlands (X.L.)."}],"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, the Netherlands (M.S., K.L.C., P.H.R., M.H.A.B.)."}],"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, the Netherlands (M.S., K.L.C., P.H.R., M.H.A.B.)."},{"name":"VarmX B.V, Leiden, the Netherlands (P.H.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2482-0412","authenticated-orcid":true,"given":"Gerry A.F.","family":"Nicolaes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8164-817X","authenticated-orcid":true,"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, the Netherlands (M.S., K.L.C., P.H.R., M.H.A.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(47)91941-7"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03622.x"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.377168"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14487"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V76.1.1.1"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0041-0101(79)90245-9"},{"key":"e_1_3_5_8_2","first-page":"825","article-title":"Purification and characterization of a prothrombin activator from the venom of the Australian brown snake, Pseudonaja textilis textilis.","volume":"17","author":"Masci PP","year":"1988","unstructured":"Masci, PP, Whitaker, AN, de Jersey, J. 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