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  1. 050 医学部, 大学院医学系研究科
  2. 0501 学術論文

Recombinant gamma T305A fibrinogen indicates severely impaired fibrin polymerization due to the aberrant function of hole 'a' and calcium binding sites

http://hdl.handle.net/10091/18411
http://hdl.handle.net/10091/18411
5e599474-4276-418e-8250-0a4894958dca
名前 / ファイル ライセンス アクション
Recombinant_gamma_T305A.pdf Recombinant_gamma_T305A.pdf (1.1 MB)
Item type 学術雑誌論文 / Journal Article(1)
公開日 2015-06-02
タイトル
タイトル Recombinant gamma T305A fibrinogen indicates severely impaired fibrin polymerization due to the aberrant function of hole 'a' and calcium binding sites
言語
言語 eng
DOI
関連識別子 https://doi.org/10.1016/j.thromres.2014.06.002
関連名称 10.1016/j.thromres.2014.06.002
キーワード
主題 hypodysfibrinogenemia, fibrin polymerization, high affinity calcium binding sites, hole 'a', D:D interaction sites
資源タイプ
資源 http://purl.org/coar/resource_type/c_6501
タイプ journal article
著者 Ikeda, Minami

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en Ikeda, Minami

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Kobayashi, Tamaki

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en Kobayashi, Tamaki

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Arai, Shinpei

× Arai, Shinpei

en Arai, Shinpei

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Mukai, Saki

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en Mukai, Saki

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Takezawa, Yuka

× Takezawa, Yuka

en Takezawa, Yuka

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Terasawa, Fumiko

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Okumura, Nobuo

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信州大学研究者総覧へのリンク
氏名 Okumura, Nobuo
URL http://soar-rd.shinshu-u.ac.jp/profile/ja.OVnmgCkh.html
出版者
出版者 PERGAMON-ELSEVIER SCIENCE LTD
引用
内容記述 THROMBOSIS RESEARCH. 134(2):518-525 (2014)
書誌情報 THROMBOSIS RESEARCH

巻 134, 号 2, p. 518-525, 発行日 2014-08
抄録
内容記述 Introduction: We examined a 6-month-old girl with inherited fibrinogen abnormality and no history of bleeding or thrombosis. Routine coagulation screening tests showed a markedly low level of plasma fibrinogen determined by functional measurement and also a low level by antigenic measurement (functional/antigenic ratio = 0.295), suggesting hypodysfibrinogenemia. Materials and methods: DNA sequence analysis was performed, and gamma T305A fibrinogen was synthesized in Chinese hamster ovary cells based on the results. We then functionally analyzed and compared with that of nearby recombinant gamma N308K fibrinogen. Results: DNA sequence analysis revealed a heterozygous gamma T305A substitution (mature protein residue number). The gamma T305A fibrinogen indicated markedly impaired thrombin-catalyzed fibrin polymerization both in the presence or absence of 1 mM calcium ion compared with that of gamma N308K fibrinogen. Protection of plasmin degradation in the presence of calcium ion or Gly-Pro-Arg-Pro peptide (analogue for so-called knob 'A') and factor XIIIa-catalyzed fibrinogen crosslinking demonstrated that the calcium binding sites, hole 'a' and D:D interaction sites were all markedly impaired, whereas gamma N308K was impaired at the latter two sites. Molecular modeling demonstrated that gamma T305 is localized at a shorter distance than gamma N308 from the high affinity calcium binding site and hole 'a'. Conclusion: Our findings suggest that gamma T305 might be important for construction of the overall structure of the. module of fibrinogen. Substitution of gamma T305A leads to both dysfibrinogenemic and hypofibrinogenemic characterization, namely hypodysfibrinogenemia. We have already reported that recombinant gamma T305A fibrinogen was synthesized normally and secreted slightly, but was significantly reduced.
資源タイプ(コンテンツの種類)
ISSN
収録物識別子タイプ PISSN
収録物識別子 0049-3848
書誌レコードID
収録物識別子タイプ NCID
収録物識別子 AA00863148
PubMed
識別子タイプ PMID
関連識別子 https://pubmed.ncbi.nlm.nih.gov/24968960
関連名称 24968960
権利
権利情報 © 2015, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
出版タイプ
出版タイプ AM
出版タイプResource http://purl.org/coar/version/c_ab4af688f83e57aa
WoS
URL http://gateway.isiknowledge.com/gateway/Gateway.cgi?&GWVersion=2&SrcAuth=ShinshuUniv&SrcApp=ShinshuUniv&DestLinkType=FullRecord&DestApp=WOS&KeyUT=000341309200049
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