An engineered fibrinogen variant A alpha Q328,366P does not polymerise normally, but retains the ability to form alpha cross-links
DC Field | Value | Language |
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dc.contributor.author | Park, Rojin | - |
dc.contributor.author | Ping, Lifang | - |
dc.contributor.author | Song, Jaewoo | - |
dc.contributor.author | Seo, Joo-Young | - |
dc.contributor.author | Choi, Tae-Youn | - |
dc.contributor.author | Choi, Jong-Rak | - |
dc.contributor.author | Gorkun, Oleg V. | - |
dc.contributor.author | Lord, Susan T. | - |
dc.date.accessioned | 2021-08-12T01:25:13Z | - |
dc.date.available | 2021-08-12T01:25:13Z | - |
dc.date.issued | 2013-02 | - |
dc.identifier.issn | 0340-6245 | - |
dc.identifier.issn | 2567-689X | - |
dc.identifier.uri | https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/13944 | - |
dc.description.abstract | A fibrin clot is stabilised through the formation of factor XIIIa-catalysed intermolecular epsilon-lysyl-gamma-glutamyl covalent cross-links between alpha chains to form alpha polymers and between gamma chains to form gamma dimers. In a previous study we characterised fibrinogen Seoul II, a heterozygous dysfibrinogen in which a cross-linking acceptor site in A alpha chain, Gln328, was replaced with Pro (A alpha Q328P). Following on the previous study, we investigated whether the alteration of Gln residues A alpha 328 and A alpha 366 affects fibrin polymerisation and alpha chain cross-linking. We have expressed three recombinant fibrinogens: A alpha Q328P, A alpha Q366P, and A alpha Q328,366P in Chinese hamster ovary cells, purified these fibrinogens from the culture media and performed biochemical tests to see how the introduced changes affect fibrin polymerisation and alpha chain cross-linking. Thrombin-catalysed fibrin polymerisation of all variants was impaired with the double mutation being the most impaired. In contrast, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analysis showed alpha polymer formation with all three engineered proteins. This study demonstrates that A alpha Q328 and A alpha Q366 are important for normal fibrin clot formation and in the absence of residues A alpha Q328 and A alpha Q366, other Gln residues in the alpha chain can support FXIIIa-catalysed fibrin cross-linking. | - |
dc.format.extent | 8 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Schattauer | - |
dc.title | An engineered fibrinogen variant A alpha Q328,366P does not polymerise normally, but retains the ability to form alpha cross-links | - |
dc.type | Article | - |
dc.publisher.location | 독일 | - |
dc.identifier.doi | 10.1160/TH12-08-0609 | - |
dc.identifier.wosid | 000314734500007 | - |
dc.identifier.bibliographicCitation | Thrombosis and Haemostasis, v.109, no.2, pp 199 - 206 | - |
dc.citation.title | Thrombosis and Haemostasis | - |
dc.citation.volume | 109 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 199 | - |
dc.citation.endPage | 206 | - |
dc.type.docType | Article | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Hematology | - |
dc.relation.journalResearchArea | Cardiovascular System & Cardiology | - |
dc.relation.journalWebOfScienceCategory | Hematology | - |
dc.relation.journalWebOfScienceCategory | Peripheral Vascular Disease | - |
dc.subject.keywordPlus | CHAIN TRUNCATION | - |
dc.subject.keywordPlus | ACCEPTOR SITES | - |
dc.subject.keywordPlus | GAMMA-CHAIN | - |
dc.subject.keywordPlus | PLASMA-FIBRINOGEN | - |
dc.subject.keywordPlus | CLOT FORMATION | - |
dc.subject.keywordPlus | C FRAGMENTS | - |
dc.subject.keywordPlus | FACTOR-XIII | - |
dc.subject.keywordPlus | PROTEINS | - |
dc.subject.keywordPlus | MUTATION | - |
dc.subject.keywordPlus | DYSFIBRINOGEN | - |
dc.subject.keywordAuthor | Fibrin alpha chain | - |
dc.subject.keywordAuthor | cross-linking | - |
dc.subject.keywordAuthor | Glutamine acceptor | - |
dc.subject.keywordAuthor | A alpha Q328 | - |
dc.subject.keywordAuthor | A alpha Q366 | - |
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